[Changes in resistance small arteries in arterial hypertension: clinical significance and possibility of pharmacologic remission].
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Antihypertensive Agents↗
Biomedical subjects
D Rizzoni
Publications and source records attributed to D Rizzoni.
[Significance and limits of dynamic monitoring of blood pressure in the clinical assessment of hypertensive patients].
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Blood Pressure Monitoring, Ambulatory↗
Relations between cardiac and vascular structure in patients with primary and secondary hypertension.
BACKGROUND: Data on cardiac and vascular structure in secondary hypertension are generally scarce, and no data on the interrelations between cardiac mass and structural characteristics of the vessel wall, both in large and in small resistance arteries, are presently available. OBJECTIVES: The aim of this study was to investigate the relation between structural changes in subcutaneous small arteries, left ventricular mass and wall thickness of the common carotid artery in patients with primary and secondary hypertension. METHODS: Seventy-four subjects were included in the study: 11 patients with pheochromocytoma, 14 with primary aldosteronism (PA), 19 with renovascular hypertension (RVH), 18 with essential hypertension (EH) and 12 normotensive (NT) control subjects. All subjects were submitted to a biopsy of subcutaneous fat. Morphologic characteristics of subcutaneous small resistance arteries (relaxed diameter <300 microm) were directly evaluated using a micromyographic technique. All subjects were submitted to calculation of left ventricular mass index (LVMI) and common carotid artery intima-media thickness (CCIMT), using ultrasound technique. RESULTS: The correlation coefficients between the media to lumen ratio in subcutaneous small arteries (M/L) and LVMI or between M/L and CCIMT were closer in RVH than in pheochromocytoma, EH or NT; in PA the correlation coefficients were slightly less close than those in RVH. An excess prevalence of carotid plaques in RVH was observed. CONCLUSIONS: A close relation between small resistance artery morphology and cardiac or carotid artery structure may be observed in those hypertensive patients in whom the renin-angiotensin-aldosterone system is activated. In constrast, in NT, EH and pheochromocytoma no significant correlation between M/L and LVMI or CCIMT was observed.
Arterioles↗
Effects of hypotensive and non-hypotensive doses of manidipine on structure, responses to endothelin-1 and ICAM-1 production in mesenteric small resistance arteries of spontaneously hypertensive rats.
OBJECTIVE: We have evaluated the effects of a new calcium channel blocker, manidipine, given at both high, hypotensive and low, non-hypotensive doses, on vascular morphology, response to endothelin-1 and ICAM-1 production in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). METHODS: Ten SHR were treated with manidipine 3 mg/kg per day (high dose) and 10 with manidipine 0.3 mg/kg/per day (low dose). The drug was administered by gavage from the 4th to 12th weeks of age. Eighteen Wistar-Kyoto (WKY) rats and 18 SHR were kept untreated as controls. Rats were killed at 13 weeks. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of indexes of vascular structure (media thickness, wall thickness, media/lumen ratio). RESULTS: Systolic blood pressure was significantly reduced by the high dose of the drug, while no effect was observed with low-dose manidipine. A reduction in the media/lumen ratio was observed only in SHR treated with high-dose manidipine. The response to endothelin-1 in untreated SHR was significantly lower in comparison with WKY; a significant reduction was observed in SHR treated with high-dose manidipine. ICAM-1 vascular concentrations were higher in untreated SHR than in WKY controls. Both high- and low-dose manidipine reduced ICAM-1 concentrations toward normalization. CONCLUSIONS: Manidipine at high, hypotensive, but not at low, non-hypotensive doses has been proven to reduce structural alterations in mesenteric small resistance arteries, and to normalize vascular responses to endothelin-1. In addition, manidipine, at both low and high doses, may reduce ICAM-1 vascular production, thus suggesting a possible anti-atherogenic effect.
Animals↗
Reduction of cardiovascular structural changes by nifedipine GITS in essential hypertensive patients.
The aim of this study was to evaluate the effect of the calcium antagonist Nifedipine GITS in a double-blind, randomized comparison with the diuretic hydrochlorothiazide (HCTZ) on reduction of left ventricular (LV) mass and minimal vascular resistance in a group of essential hypertensives with left ventricular hypertrophy (LVH). The effects on blood pressure and on echocardiographic LV functional parameters were also analysed. After two months of randomized treatment with Nifedipine GITS or HCTZ, if diastolic blood pressure was > 90 mmHg, a combination of the two drugs was given and was continued for 24 weeks. M-mode, 2D-guided echocardiography was used to measure LV mass index (LVMI) according to the "Penn convention". Minimal vascular resistance was measured in the forearm, from arterial pressure and maximal blood flow, using a strain gauge plethysmography. All examinations were performed before and after 8 and 24 weeks of treatment. Changes in LVMI were analysed at 8 weeks and at 24 weeks in patients receiving monotherapy ("according to protocol" analysis), and also at the end of treatment in patients taking Nifedipine or HCTZ monotherapy or the combination of the two drugs ("intention to treat" analysis). Both Nifedipine and HCTZ significantly reduced systolic and diastolic blood pressure (p < 0.001), without any significant difference between the two drug treatments. Heart rate was not significantly modified by either treatment. A progressive decrease in LVMI was observed after 8 and 24 weeks of treatment with Nifedipine monotherapy (ANOVA, p = 0.03), while the decrease in LVMI during HCTZ treatment did not progress further at 24 weeks (ANOVA, p = 0.49). A significant reduction of minimal vascular resistance was observed in patients treated with Nifedipine GITS monotherapy (ANOVA, p = 0.001), but not in the HCTZ group (ANOVA, p = 0.06). Comparison of changes of forearm minimal vascular resistance, considering baseline values, could demonstrate a greater effect during Nifedipine monotherapy as compared to HCTZ monotherapy. In conclusion, in a group of hypertensive patients with LVH, treatment for 24 weeks with Nifedipine GITS alone or in combination with HCTZ induced a significant reduction in LVMI and of forearm vascular structural changes, as evaluated by minimal vascular resistance. The decrease of minimal vascular resistance was significantly greater in patients treated with Nifedipine monotherapy, as compared to those given HCTZ.
Adult↗
Various ways of calculating echocardiographic left ventricular mass and their relative prognostic values.
OBJECTIVE: To compare the calculations of left ventricular mass according to thick-wall [American Society of Echocardiography (ASE) and Penn convention] and thin-wall (Wikstrand formula) models. METHODS: We have reexamined the data from the cross-sectional study on the general population sample of Vobarno and from a prospective longitudinal study of hypertensive patients assessing the prognostic significance of changes in left ventricular mass during a follow-up period of 10 years on average (Brescia population). RESULTS: For the Vobarno and Brescia populations, we found a close relationship between values of left ventricular mass calculated by using a thin-wall ellipsoidal model (Wikstrand formula) and those calculated using a thick-wall model with Penn convention or ASE left ventricle measurements (r = 0.99, for both the Vobarno and Brescia populations). Highest values of Penn left ventricle mass were slightly underestimated by use of the thin-wall formula. The numbers of nonfatal cardiovascular events and the relative risks, evaluated by Cox proportional hazard models for 151 patients seen at follow-up did not differ for patients with persistence of left ventricular hypertrophy (LVH), those with regression of LVH, and those with normal left ventricle mass, both at baseline and at follow-up, when these different ways of measuring left ventricle mass and partition values for LVH were used. CONCLUSIONS: The calculation of left ventricle mass according to the ASE recommendations or to the Penn convention, both of which are based on the assumption that the left ventricle can be represented by a prolate ellipsoid with both the internal and external long axes twice the short axis, produces results similar to those obtained using an alternate formula for the calculation of left ventricle mass, considering wall thickness constant around the ellipsoidal cavity. The cardiovascular risk stratification, in relation both to baseline left ventricular mass and to its change during long-term antihypertensive treatment, does not differ significantly among the results of these three different calculations.
Antihypertensive Agents↗
Power spectral analysis of the heart rate in hypertensive patients with and without left ventricular hypertrophy: the effect of a left ventricular mass reduction.
OBJECTIVE: The aim of this study was to evaluate the spectral analysis of the heart rate in normotensive subjects and in hypertensive patients with and without left ventricular hypertrophy (LVH), under basal conditions and after a reduction in left ventricular mass. SUBJECTS AND METHODS: In 12 normotensive subjects and 22 hypertensive patients (14 with and eight without LVH), we performed 24 h electrocardiogram Holter monitoring, ambulatory blood pressure monitoring and an echocardiographic study. Sequences of 512 R-R intervals, during daytime, afternoon and night-time periods, were taken for an evaluation of spectral analysis (Box-Jenkins method). We then calculated the absolute and percentage power spectral density of the peak centred at 0.10 Hz (low-frequency peak) and at 0.25 Hz (high-frequency peak). RESULTS: At baseline, a daytime to night-time decrease in the low-frequency peak was detected in normotensives (P < 0.01) and in hypertensives without LVH (P < 0.01), while no change was observed in hypertensives with LVH. The power spectral density low-frequency peak during the daytime and night-time was significantly greater in hypertensives with LVH than in those without LVH (P < 0.001) and in normotensive subjects (P < 0.001). Fourteen of these patients with LVH were given effective long-term antihypertensive treatment and were studied again 20 days after the treatment had been withdrawn, when blood pressure had increased to pretreatment values. In eight patients showing a reduction in LVH, we found a significant decrease in the power spectral density low-frequency peak and an increase in the high-frequency peak during daytime and night-time in respect to basal conditions, and circadian variations in the spectral indices of heart rate variability were restored. In contrast, in six patients without reversal of LVH, the power spectral density low-frequency peak did not change in respect to basal conditions and remained significantly higher in comparison with the patients with LVH regression. CONCLUSION: A reduction in LVH may be associated with restoration of daytime to night-time cardiac autonomic control, as evaluated by a power spectral analysis of the heart rate.
Adolescent↗
The smoothness index: a new, reproducible and clinically relevant measure of the homogeneity of the blood pressure reduction with treatment for hypertension.
OBJECTIVE: To introduce a new method, the smoothness index, for assessing the homogeneity of 24 h blood pressure reduction by antihypertensive treatment and to compare it with the trough : peak ratio; and to assess the ability of both indices to predict a reduction in the left ventricular mass index induced by treatment. PATIENTS AND METHODS: In 174 patients with essential hypertension and left ventricular hypertrophy, enrolled in the Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation (SAMPLE), aged 20-65 years, we measured clinic blood pressure, 24 h ambulatory blood pressure and the left ventricular mass index (echocardiography) before and after treatment with lisinopril at 20 mg with the addition of 12.5 or 25 mg hydrochlorothiazide as needed to reach a sufficient blood pressure reduction. The following parameters were computed for systolic and diastolic ambulatory blood pressure: (1) hourly and 24 h blood pressure averages (+/- SD) at baseline and after 3 and 12 months of treatment; (2) hourly blood pressure changes from baseline after 3 and 12 months of treatment, and their average (+/- SD) over 24 h; (3) the trough : peak ratio after 3 and 12 months of treatment; and (4) the smoothness index after 3 and 12 months of treatment Similar calculations were also performed at the end of a final study month during which active treatment was withdrawn and placebo was substituted (n = 164). RESULTS: The smoothness index for systolic and diastolic ambulatory blood pressure computed after 3 months of treatment was more closely related to its corresponding values after 12 months of treatment than the trough : peak ratio values computed after the same time periods were (r = 0.68 versus 0.38 for systolic and 0.68 versus 0.42 for diastolic blood pressure, respectively). The smoothness index showed an inverse correlation with the 24 h standard deviation of systolic and diastolic blood pressure (r = -0.25 and -0.16, P < 0.01 and < 0.05, respectively, for 12 months of treatment), while the trough : peak ratio did not (r = -0.01 to -0.12, NS). A treatment-induced reduction in the left ventricular mass index was related to the smoothness index for systolic and diastolic blood pressure (r = -0.35 and -0.32, P< 0.001 with 12 months of treatment), but not to the corresponding trough : peak ratios. CONCLUSIONS: The smoothness index identifies the occurrence of a balanced 24 h blood pressure reduction with treatment and correlates with the favourable effects of treatment on left ventricular hypertrophy better than the commonly used trough : peak ratio.
Adult↗
Structural association between the carotid artery and the left ventricle in a general population in Northern Italy: the Vobarno study.
OBJECTIVE: To evaluate the interrelationships between structural alterations in the carotid arteries and left ventricular geometric patterns in a middle-aged general population. DESIGN AND METHODS: We studied 223 untreated subjects (106 females, 117 males; aged 48-64 years) living in a small town in Northern Italy (Vobarno, Brescia), using a cross-sectional design. The left ventricular mass index was assessed by echocardiography, while the intima-media thickness and the occurrence of plaque were evaluated by ultrasound. Blood pressure was determined by clinic measurements and by 24 h noninvasive ambulatory blood pressure monitoring. RESULTS: According to the presence of left ventricular hypertrophy (left ventricular mass index > 50 g/m2.7 in males and > 47 g/m2.7 in females) or concentric left ventricular remodelling (normal left ventricular mass index and relative wall thickness > 0.42), the subjects were divided into four groups: 124 subjects with normal left ventricular geometry, 73 subjects with left ventricular hypertrophy (55 with eccentric and 18 with concentric hypertrophy) and 26 subjects with concentric remodelling. The common carotid intima-media thickness and cross-sectional area were significantly greater in the subjects with concentric left ventricular hypertrophy (analysis of variance, P< 0.05) than in those with normal left ventricular geometry. A significantly higher number of plaques was observed in subjects with concentric and eccentric left ventricular hypertrophy. CONCLUSIONS: In a general population of unselected middle-aged subjects, the presence of concentric left ventricular hypertrophy was associated with an increase in intima-media thickness and with the presence of plaque in the carotid arteries, possibly contributing to the worse prognosis observed in this group of patients.
Aged↗
Effects of candesartan cilexetil and enalapril on structural alterations and endothelial function in small resistance arteries of spontaneously hypertensive rats.
It was previously observed that a significant regression of structural alterations and endothelial dysfunction in mesenteric small arteries of spontaneously hypertensive rats (SHRs) may be obtained after therapy with angiotensin-converting enzyme (ACE) inhibitors. It is not clear whether angiotensin II-type 1 receptor blockers may share this properties. We evaluated the effects of the ACE inhibitor enalapril and of the angiotensin II-receptor blocker candesartan cilexetil on structural alterations of mesenteric small resistance arteries, on cardiac mass, and on endothelial function in SHRs. Seventy-three rats were included in the study. Sixteen SHRs were treated with enalapril and 21 with candesartan cilexetil, whereas 18 Wistar-Kyoto (WKY) and 18 SHRs were untreated. Enalapril and candesartan cilexetil were administered in the drinking water from weeks 4 to 12 of age. Blood pressure was measured noninvasively every week. The rats were killed at the end of the treatment period, after 3 or 4 days of therapeutic washout. Heart weight/body weight ratio (HW/BW) was measured. Mesenteric arterioles were dissected and mounted on a micromyograph (Mulvany's technique). Then the media-to-lumen ratio (M/L) was evaluated. In addition, endothelium-dependent and endothelium-independent relaxation was evaluated by dose-response curves to acetylcholine (in the presence or absence of a bradykinin-receptor blocker and of indomethacin) and sodium nitroprusside. Systolic blood pressure was significantly reduced by both drugs, compared with untreated SHRs, although the hypotensive effect was greater with enalapril than with candesartan cilexetil. A significant reduction of M/L of mesenteric small arteries and of HW/BW was observed in SHRs treated with candesartan cilexetil or enalapril. A significant improvement of endothelial function, as evaluated by a dose-response to acetylcholine, was observed. The acetylcholine-induced vasodilatation was similar after addition to the organ bath of a selective blocker of bradykinin receptors, thus suggesting a minor role (if any) of the increased local availability of bradykinin, as a consequence of inhibition of ACE, in the improvement of endothelial function observed after enalapril treatment. In addition to a satisfactory antihypertensive effect observed with both drugs, candesartan cilexetil and enalapril were proven to be equally effective in reducing structural alterations in mesenteric small resistance arteries, in normalizing cardiac mass, and in improving endothelial function. The inhibition of bradykinin breakdown does not seem to be involved in the improvement of endothelial dysfunction observed with ACE inhibitors.
Acetylcholine↗
Endothelial dysfunction in hypertension is independent from the etiology and from vascular structure.
The aim of our study was to evaluate the relationships between endothelial function, small resistance artery structure, and blood pressure in patients with primary or secondary hypertension. Sixty subjects were included in the study: 9 patients with pheochromocytoma, 10 with primary aldosteronism, 17 with renovascular hypertension, and 13 with essential hypertension with 11 normotensive subjects who served as controls. Clinic and 24-hour ambulatory blood pressure (ABPM) were evaluated. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph and the media/lumen ratio was calculated. A dose-response curve to acetylcholine was performed at cumulative concentrations from 10(-9) to 10(-5) mol/L. The vasodilator response to acetylcholine was similarly impaired in the four groups of hypertensive patients (ANOVA P<.05 versus normotensive controls), without any significant difference among them. In subcutaneous small arteries of patients with either primary aldosteronism or renovascular hypertension, a marked increase in media:lumen ratio was observed, while in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in essential hypertension. No significant correlation between media-lumen ratio or clinic blood pressure and maximum acetylcholine-induced vasodilatation was observed. On the contrary, a significant, albeit not very close, correlation between ABPM values and maximum acetylcholine-induced vasodilatation was observed (r=34, P<.05 with 24-hour systolic blood pressure, r=0.36, P<.05 with 24-hour diastolic blood pressure). In conclusion, endothelial dysfunction seems to be independent from the degree of vascular structural alterations and from the etiology of hypertension, and it is probably more linked to the hemodynamic load.
Acetylcholine↗
Effects of losartan and enalapril on small artery structure in hypertensive rats.
We evaluated the effects on cardiovascular structure of the angiotensin-converting enzyme (ACE) inhibitor enalapril and of the angiotensin II receptor blocker losartan, administered either at hypotensive or nonhypotensive dosage in spontaneously hypertensive rats (SHR). SHR were treated from ages 4 to 12 weeks with low-dose (1 mg x kg(-1) x d(-1)) enalapril, low-dose (0.5 mg x kg(-1) x d(-1)) losartan, high-dose (25 mg x kg(-1) x d(-1)) enalapril, or high-dose (15 mg x kg(-1) x d(-1)) losartan. Untreated WKY and SHR were also studied. Rats were killed at 13 weeks of age, and the heart was weighed. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of media thickness and lumen diameter. In fixed arteries, cell volume, number of cells per segment length, and number of cell layers were measured using the unbiased "disector" method. Systolic blood pressure was significantly reduced by the high doses of both drugs, but the hypotensive effect was greater with enalapril than with losartan (P<0.05). In the high-dose enalapril and losartan groups, there were similar reductions in relative left ventricular mass, media/lumen ratio, and number of cell layers of resistance arteries; however, there were no differences in the cell volume or number of cells per segment length of resistance arteries. Low-dose enalapril did not affect systolic blood pressure or any of the structural parameters. The results show that the hypotensive effects of both losartan and enalapril were associated with outward remodeling of resistance arteries at the cellular level. The effect of losartan on resistance artery structure was equal to that of enalapril, despite the smaller hypotensive effect.
Animals↗
Prolonged effects of short-term fosinopril on blood pressure and vascular morphology and function in rats.
The aim of this study was to evaluate the delayed effects of an angiotensin converting enzyme (ACE) inhibitor on blood pressure and on structural and functional alterations in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). The ACE inhibitor fosinopril (25 mg/kg/day) was administered according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n = 12), in a second group from 8 to 12 weeks of age (n = 15), and in a third group from 4 to 12 weeks of age (n = 12). Eighteen untreated SHR and 18 untreated Wistar-Kyoto rats served as controls. About half the animals in each group were killed at 13 weeks of age, and the remaining were killed at 38 weeks of age. After death, relative left ventricular mass (left ventricular weight/body weight) was calculated. Vascular morphology (media:lumen ratio) and function (responses to norepinephrine and acetylcholine) in mesenteric small resistance arteries were then assessed using a micromyographic technique. Short-term fosinopril, given either before or after the development of hypertension, persistently reduced (but did not normalize) systolic blood pressure, vascular structural alterations, and reactivity to norepinephrine in mesenteric resistance arteries in SHR. These favorable effects were maintained at least for 26 to 30 weeks after treatment withdrawal. The endothelium-dependent vasodilator response to acetylcholine was improved at 13 but not at 38 weeks of age, in treated SHR. Therefore, the vascular response to norepinephrine seems to be dependent mainly on the structure of the vessels, whereas endothelial function is probably more linked to the hemodynamic load.
Angiotensin-Converting Enzyme Inhibitors↗
Effects of long-term antihypertensive treatment with lisinopril on resistance arteries in hypertensive patients with left ventricular hypertrophy.
OBJECTIVE: To evaluate the effects of long-term antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril on structural alterations and the endothelial function of small resistance arteries in hypertensive patients with left ventricular hypertrophy. METHODS: Fourteen patients with left ventricular hypertrophy were treated for 3 years with a lisinopril-based regimen. Patients underwent an echocardiographic evaluation of left ventricular mass index at baseline, during the first and third years of treatment. At the end of the treatment period, subcutaneous small resistance arteries (obtained by biopsy of the subcutaneous fat from the gluteal region) were dissected and mounted on a micromyograph (Mulvany's technique); the media : lumen ratio was then calculated. Data obtained were compared with those observed for 14 untreated essential hypertensive patients and 14 normotensive subjects, age- and sex-matched. RESULTS: In the present study, a significantly lower media : lumen ratio was observed in treated compared with untreated hypertensive patients, although it remained significantly higher than that in normotensive subjects. In treated hypertensive patients a significant reduction in clinic blood pressure was observed. However, their blood pressure remained significantly higher than that in normotensive subjects. Significant correlations between the media : lumen ratio and blood pressure, left ventricular mass index or changes in left ventricular mass index during treatment were observed. The response to acetylcholine administration was reduced in untreated hypertensives compared with that in normotensives. In patients treated with lisinopril, the vasodilatation obtained with the two higher doses of acetylcholine was greater than that in untreated hypertensives, thus suggesting an improvement of endothelial function. CONCLUSIONS: Long-term therapy based on lisinopril was associated with a smaller media : lumen ratio in the subcutaneous small resistance arteries of hypertensive patients with left ventricular hypertrophy. Our retrospective study confirms previous findings obtained in prospective studies with other angiotensin converting enzyme inhibitors. Endothelial function was probably improved by lisinopril therapy.
Aged↗
Structural changes of small resistance arteries in spontaneously hypertensive rats after treatment with various doses of lacidipine.
OBJECTIVE: To evaluate the modifications of the morphology of mesenteric small resistance vessels in spontaneously hypertensive rats (SHR) induced by lacidipine treatment. METHODS: Lacidipine was administered at three different dosages, 20, 10, and 0.3 mg/kg per day. Fifty rats were studied. Nine SHR and 11 Wistar-Kyoto (WKY) rats were not treated. Each lacidipine dose was administered to 10 SHR. The drug and the placebo were administered by gavage from age 4 to age 12 weeks. The blood pressure was measured noninvasively every week. The animals were killed when they were aged 13 weeks, and the relative left ventricular mass (left ventricular weight plus septum weight/body weight) was calculated. Small mesenteric resistance vessels were dissected and mounted on a micromyograph (Mulvany's technique), and morphological parameters of the vessels were studied (media thickness and media: lumen ratio). RESULTS: The systolic blood pressure of SHR administered 20 and 10 mg/kg lacidipine per day was reduced significantly during the treatment period, whereas that of rats treated with 0.3 mg/kg lacidipine per day did not change. A significant reduction in media: lumen ratio was observed for all three groups of treated rats, including those to which 0.3 mg/kg lacidipine per day had been administered, and no reduction in systolic blood pressure could be detected. The relative left ventricular mass was reduced significantly only in rats to which 20 and 10 mg/kg lacidipine per day had been administered. CONCLUSION: A significant reduction in magnitude of vascular structural alternations was observed even in SHR treated with a low, nonhypotensive dose of lacidipine.
Animals↗
The vasoconstriction induced by endothelin-1 is mediated only by ET(A) receptors in mesenteric small resistance arteries of spontaneously hypertensive rats and Wistar Kyoto rats.
OBJECTIVE: To evaluate the functional responses of mesenteric small resistance arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rat controls to endothelin-1 (ET-1), in the presence and absence of an ET(A) receptor antagonist drug as well as to an ET(B) receptor agonist. METHODS: Twenty rats aged 12 weeks were studied. They were 10 SHR and 10 WKY rats. Mesenteric small resistance arteries (relaxed diameter 100-180 microm) were dissected and mounted on a micromyograph (Mulvany's technique). A dose-response curve for response to ET-1 was plotted for cumulative concentrations (from 10(-11) to 10(-8) mol/l) in the presence and absence of 10(-6) mol/l FR 139317 (a selective antagonist of ET(A) receptors). In addition, the effects of 10(-7) mol/l N-succinyl-[Glu9, Ala11,15]-endothelin 1 fragment 8-21 (IRL 1620, a selective agonist of ET(B) receptors) were evaluated. RESULTS: The response of ET-1 was greater in WKY rats than it was in SHR. Almost all the vasoconstrictor effect of ET-1 could be prevented by addition of FR 139317, whereas the agonist of ET(B) receptors had no effect (no change in active force). CONCLUSIONS: The contractile effects of ET-1 on mesenteric small resistance arteries of SHR and WKY rats are mediated mostly by ET(A) receptors, whereas ET(B) receptors play a minor role, if any. It is possible, however, that a vasoconstrictor effect of ET(B) receptors on the smooth muscle could be masked by the concomitant stimulation of endothelial ET(B) vasodilator receptors.
Animals↗
Alpha-adducin gene polymorphism and cardiovascular phenotypes in a general population.
BACKGROUND: Previous studies have shown that molecular variants of the cytoskeletal protein adducin may be involved in regulation of blood pressure both in genetic rat hypertension and in human essential hypertension. OBJECTIVE: To investigate the relationship of genetic polymorphism of alpha-adducin with blood pressure, cardiovascular structure, and some biochemical indexes of cardiovascular risk in a sample of general population. DESIGN AND METHODS: A sample of 246 subjects (124 men and 122 women, aged 57.7+/-3.7 years) was randomly chosen from a middle-aged population. Twenty-four-hour ambulatory blood pressure, as well as left ventricular mass (by echocardiographic methods) and carotid wall thickness (by B-mode ultrasound methods) were measured. DNA was extracted from peripheral blood samples; the Gly460Trp diallelic variant of human alpha-adducin was genotyped by polymerase chain reaction amplification and then allele-specific oligo hybridization. RESULTS: A trend toward higher 24 h ambulatory blood pressure values in subjects not treated with antihypertensive drugs was observed among carriers of Trp460 allele, although the differences did not attain statistical significance (at closest, P = 0.066 for a dominant effect of Trp460 on systolic blood pressure). When blood pressure was considered a dichotomous variable, allowing the inclusion of treated hypertensives), a higher prevalence of Trp460 allele among hypertensives was observed (0.188 versus 0.106 among normotensives, P= 0.02). There was no evidence of association either of left ventricular mass or of common carotid wall thickness with Gly460Trp polymorphism. CONCLUSIONS: In this sample of a general population, the relationship of a genetic polymorphism of alpha-adducin with blood pressure values was rather weak. However, a population-based case-control analysis indicated that there was an association between Trp460 allele and hypertension, with a relative risk for subjects carrying at least one Trp460 allele of approximately 1.6. Further investigation of larger and different population samples in order to assess the role of adducin gene polymorphism as a marker of genetic predisposition to the development of hypertension is warranted.
Aged↗
Relationships of cardiac function and structure to blood pressure rhythms.
It is well known that hemodynamic load is one of the most important determinants of cardiac structure and function. Circadian variations in blood pressure (BP) values are usually accompanied by consensual changes in peripheral resistance and/or cardiac output. In recent years, in hypertensive patients with left ventricular hypertrophy (LVH), a reduction in the circadian variations of BP and, in particular, a lack of nocturnal decline were observed; patients with only a small reduction in BP or none at all during the night were considered "non-dippers." In patients in whom a regression of LVH was obtained after prolonged antihypertensive therapy, restoration of the circadian rhythm of BP was also observed. However, the division of patients into "dippers" and "non-dippers" is arbitrary and poorly standardized and repeatable, and in the recent SAMPLE study, most hypertensive patients with LVH were dippers. Therefore, we should be particularly cautious about the conclusions drawn using this index. On the other hand, in patients with LVH, reduced activity of the low pressure cardiopulmonary baroreceptors and impaired day-to-night modulation of autonomic nervous system activity were observed. Therefore, cardiac structural alterations may possibly impair BP modulation; on the other hand, the opposite could also be true: a primarily altered BP modulation, through a persistently elevated afterload, could increase cardiac mass. Therefore, the interrelationships between cardiac structure and BP modulation are complex, and as a result, new and more specific methods of evaluation circadian changes in BP are needed to better clarify their reciprocal influences.
Blood Pressure↗