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Biomedical subjects

M Castellano

Publications and source records attributed to M Castellano.

At least 37 records · Page 2Linked to original sources
PubMed2001

The smoothness index, but not the trough-to-peak ratio predicts changes in carotid artery wall thickness during antihypertensive treatment.

BACKGROUND: It has recently been demonstrated that the smoothness index (SI) (the ratio between the average of the blood pressure changes computed for each hour of the recording and its standard deviation), a new and reproducible measure of the homogeneity of blood pressure reduction by antihypertensive treatment, has evident advantages over trough-to-peak ratio (T/P) in the prediction of the regression of left ventricular hypertrophy. Therefore we considered it to be worthwhile to compare the ability of SI and T/P to predict changes of the carotid artery intima-media thickness (IMT) during pharmacological treatment in patients with essential hypertension. METHODS: In 100 patients with essential hypertension, 24 h ambulatory blood pressure and carotid artery IMT were measured after 3 weeks of therapeutic wash-out and after 12 months of antihypertensive treatment (calcium antagonists, diuretics, angiotensin converting enzyme (ACE) inhibitors or beta-blockers). The homogeneity of the effect of treatment over blood pressure was evaluated by computing T/P and SI. RESULTS: Twenty-four hour blood pressure was significantly reduced by therapy, while, on average, a small but significant increase in indices of carotid artery wall thickness was observed. However, IMT was clearly reduced in patients with high SI. Statistically significant correlations were observed between changes in indices of carotid artery IMT during therapy and SI. No significant correlation was observed between indices of carotid artery morphology and T/P, basal 24 h blood pressure or changes in blood pressure during therapy. CONCLUSIONS: SI, but not T/P is the predictor of changes in carotid artery wall thickness. The information provided by SI is independent from basal blood pressure values. For carotid artery morphology, the smoothness of blood pressure reduction is even more important than its absolute change.

Adult↗
PubMed2000

Time course of apoptosis in small resistance arteries of spontaneously hypertensive rats.

OBJECTIVE: The time course of programmed cell death (apoptosis) in the vasculature of spontaneously hypertensive rats (SHRs) is still unclear. Moreover, no data are presently available about the possible inter-relationships between apoptosis and vascular remodelling. The aim of this study was to investigate the mesenteric small resistance arteries and large arteries (aortas) of SHRs and normotensive Wistar-Kyoto (WKY) rats at different ages, before and after the development of overt hypertension. METHODS: Twenty-four SHRs (4, 8 or 12 weeks old) and 24 age-matched WKY rats were included in the study. Blood pressure was measured non-invasively. Rats were killed by decapitation and segments of aortas and small mesenteric arteries were dissected free from the surrounding tissue. Mesenteric arteries were mounted on a micromyograph and structural characteristics were measured (media thickness, media:lumen ratio, etc.). Apoptotic cells in the tunica media of large and small vessels were then stained using modified TdT-mediated dUTP Nick-End Labeling (TUNEL). RESULTS: At 4 weeks of age no difference in the blood pressure and percentage of apoptosis in mesenteric arteries between SHRs and WKY rats was detected; however, the media:lumen ratio of mesenteric small resistance arteries was significantly greater in SHRs. At 8 and 12 weeks of age systolic blood pressure, media:lumen ratio and apoptosis rate in mesenteric small arteries was significantly higher in SHRs. The rate of apoptosis in the aortas was similar in the two strains at all three ages. CONCLUSIONS: An increased prevalence of apoptosis was observed in mesenteric small arteries of 8- and 12-week-old SHRs. It is possible that apoptosis may exert a role in small resistance artery remodelling during the development and establishment of hypertension.

Aging↗
PubMed2000

Enhanced vascular reactivity in the sympathectomized rat: studies in vivo and in small isolated resistance arteries.

OBJECTIVE: In the conscious rat, sympathectomy (6-hydroxydopamine pretreatment, 100 mg/kg intraperitoneally, twice in the previous 5-6 days) induces, among various homeostatic modifications, the frequent occurrence of sudden and wide oscillations of blood pressure. Since one of the mechanisms underlying this, as yet unexplained, phenomenon may be an enhanced vascular reactivity, we tested the hypothesis that sympathectomized rats exhibit such a hyper-reactivity. We examined the response to a variety of vasoactive agents both in vivo (chronically instrumented conscious animals) and in vitro (small isolated resistance arteries). DESIGN AND METHODS: Wistar-Kyoto sympathectomized rats (6-hydroxydopamine pretreatment, n = 19) and control rats (vehicle pretreatment, n = 23) were studied. In conscious animals, concentration-blood pressure response curves to intra-venous bolus injections of vasopressin, phenylephrine and angiotensin II were obtained. In isolated vessels, concentration-wall tension response curves were obtained for norepinephrine, phenylephrine, vasopressin, serotonin and potassium. Vasodilator responses to acetylcholine (with or without L-NAME), bradykinin and sodium nitroprusside were also evaluated after precontraction with norepinephrine (mesenteric arteries) or vasopressin (cerebral arteries). RESULTS: In sympathectomized rats in vivo the pressor responses to vasopressin, phenylephrine and angiotensin II were significantly larger than in control rats, the difference amounting to 46.5, 40.2 and 57.1%, respectively (all P < 0.05). In vitro, the vascular reactivity of isolated cerebral arteries was similar in sympathectomized and control rats. In contrast, the mesenteric arteries showed significantly increased contractions in sympathectomized compared to control rats in response to norepinephrine, phenylephrine and vasopressin but not to serotonin and potassium, whereas the vasodilator responses to acetylcholine and sodium nitroprusside (but not to bradykinin and acetylcholine+L-NAME) were reduced. CONCLUSIONS: In conclusion, we showed that sympathectomy produces complex alterations of vascular reactivity both in vivo and in isolated vessels, which shift the balance of the sensitivity of the vessel between vasoconstrictor and vasodilating agents towards an increased constriction. These results are unlikely to simply reflect denervation supersensitivity; their underlying receptor, post-receptor and/or contractile mechanisms are yet to be identified.

Animals↗
PubMed2000

Changes in midwall systolic performance and cardiac hypertrophy reduction in hypertensive patients.

OBJECTIVE: To investigate changes in left ventricular (LV) performance, as evaluated by measurement of midwall LV fractional shortening (FS), after reduction of cardiac hypertrophy. DESIGN AND METHODS: Echocardiographic evaluation of LV anatomy and function was performed by M-mode echocardiography at baseline, after long-term antihypertensive therapy, and after treatment withdrawal in 68 asymptomatic hypertensive patients (50 males, 18 females, age range 22-62 years). Patients were divided according to the presence of LV hypertrophy (LVH) at baseline (LV mass index, LVMI, > or = 51 g/m(2.7)). RESULTS: At baseline patients with concentric (relative wall thickness > 0.44) LV hypertrophy (n = 38) or remodelling (n = 7) had reduced midwall shortening with respect to patients with normal LV geometry (n = 4) or eccentric LVH (n = 19); no differences were observed for endocardial FS. After long-term treatment (average 15 months), in 11 patients LV mass remained within normal limits, in 45 patients LVH reduction was obtained, while in 12 patients LV mass remained persistently elevated. Midwall FS was significantly increased in patients with reduction of LVH both during treatment and after withdrawal of treatment, while it remained significantly lower in patients with persistently elevated LV mass. Changes in midwall fractional shortening were independently associated with modifications in relative wall thickness (P < 0.00001), with changes in end-diastolic dimensions (P < 0.0001) and those of LVMI (P< 0.02) as shown by multivariate analysis. CONCLUSION: LV midwall systolic performance significantly improved after reduction of LVH, even in the presence of high blood pressure values. Modifications in relative wall thickness are more independently associated with changes, in LV diastolic dimensions and mass, to midwall improvement

Adult↗
PubMed2000

Cellular hypertrophy in subcutaneous small arteries of patients with renovascular hypertension.

Structural alterations of small arteries in patients with essential hypertension are characterized by inward eutrophic remodeling. However, small arteries in patients with secondary hypertension, as well as in experimental models of hypertension with high circulating renin, are characterized by inward hypertrophic remodeling, which is characterized by smooth muscle cell hypertrophy in animal models. The aim of our study was to determine whether remodeling of subcutaneous small arteries in patients with secondary forms of hypertension is associated with smooth muscle cell hypertrophy and/or alterations in the elastic modulus of the vessel wall. Fifteen patients with renovascular hypertension, 9 with primary aldosteronism, and 13 with essential hypertension and 9 normotensive subjects were included in the study. A biopsy of subcutaneous fat was taken from all subjects. Small arteries were dissected, and morphology was determined on a micromyograph. Unbiased estimates of cell volume and number were made in fixed material. From the resting tension-internal circumference relation of the small arteries, the incremental elastic modulus was calculated and plotted as a function of wall stress. Blood pressure was greater in patients with essential hypertension, renovascular hypertension, or primary aldosteronism than in normotensive subjects, but no significant difference was observed among the 3 groups of hypertensive patients. The media/lumen ratio, the medial cross-sectional area, and the smooth muscle cell volume were significantly greater in patients with renovascular hypertension than in normotensive subjects and patients with essential hypertension. No difference in cell number or in the elastic properties was observed among the 4 groups of subjects. In conclusion, our data demonstrate for the first time that a pronounced activation of the renin-angiotensin-aldosterone system is associated with vascular smooth muscle cell hypertrophy in human hypertension in a manner similar to that found in animal models.

Arteries↗
PubMed1999

Functional reassessment of P16 variants using a transfection-based assay.

CDKN2A appears to be the major melanoma susceptibility gene, and is also mutated/deleted in sporadic tumours of various types including melanoma. Thus far most approaches to assessing the functionality of mutations in this gene have used in vitro methods such as CDK4 binding and kinase inhibition assays, with sometimes disparate conclusions about functional significance of some variants between studies. We have used a melanoma cell line (MM96L) with no functional p16, as the basis for a "semi-in vivo" transfection-based assay for exogenous p16 functionality based on the growth parameters of the cells and the behaviour of variant proteins after transfection of different CDKN2A cDNAs. Colony counts performed on these transfectants revealed that all but the wild type, + 24 bp ad A148T variants have a diminished ability to inhibit cell growth. All other variants detected either constitutionally in familial melanoma patients (I49T, R87P, G101W and V126D) or somatically in melanomas (N71S, and P81L), appeared functionally impaired in this assay. This diminution of function was independent of CDK4 and CDK6 binding ability. Furthermore, the predominant localization of these variants within the cell was different from that of wt p16. This mislocalization may provide an explanation for their lack of function, or alternatively, it may also be an indicator that the cells are processing unstable, misfolded p16 proteins. This novel assay for assessment of functionality of p16 variants may better reflect the role of some of these mutations in vivo, and as such is a useful adjunct to other in vitro assays.

Cell Nucleus↗
PubMed1999

A cyclin D-Cdk4 activity required for G2 phase cell cycle progression is inhibited in ultraviolet radiation-induced G2 phase delay.

Cyclin D-Cdk4 complexes have a demonstrated role in G1 phase, regulating the function of the retinoblastoma susceptibility gene product (Rb). Previously, we have shown that following treatment with low doses of UV radiation, cell lines that express wild-type p16 and Cdk4 responded with a G2 phase cell cycle delay. The UV-responsive lines contained elevated levels of p16 post-treatment, and the accumulation of p16 correlated with the G2 delay. Here we report that in UV-irradiated HeLa and A2058 cells, p16 bound Cdk4 and Cdk6 complexes with increased avidity and inhibited a cyclin D3-Cdk4 complex normally activated in late S/early G2 phase. Activation of this complex was correlated with the caffeine-induced release from the UV-induced G2 delay and a decrease in the level of p16 bound to Cdk4. Finally, overexpression of a dominant-negative mutant of Cdk4 blocked cells in G2 phase. These data indicate that the cyclin D3-Cdk4 activity is necessary for cell cycle progression through G2 phase into mitosis and that the increased binding of p16 blocks this activity and G2 phase progression after UV exposure.

Cyclin D↗
PubMed1999

Genes involved in melanoma: an overview of INK4a and other loci.

Melanoma is the most aggressive of the skin cancers and its prognosis is often poor. The only known environmental risk factor for this tumour is ultraviolet light exposure. This fact together with the existence of melanoma-prone families has prompted investigation of genetic risk factors that may be involved in melanoma development. Inactivation of the INK4a/p16 gene is known to play a role in familial cases. Data on genes or loci involved in sporadic melanoma are less definitive and require more detailed research. In addition to the INK4a locus, other genes involved in melanoma development are discussed here, in particular those genes that participate in the same functional pathway, such as CDK4 and Rb, and p53, which is regulated by the alternative product of INK4a. Evidence showing the possible location of melanoma susceptibility genes on chromosomes 1p, 6, 10q and 11q is analysed along with data showing N-ras, betacatenin, c-myc and MC1R involvement. Melanoma is a well-characterized disease in terms of its progression stages; therefore obtaining precise genetic information is crucial in the development of a stepwise model of melanoma pathogenesis.

Animals↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Chamber-specific alterations of norepinephrine uptake sites in cardiac hypertrophy.

The present study investigated local differences of sympathetic activation and sympathetic neuroeffector defects in nonhypertrophied right and hypertrophied left ventricles in a rat model with renin-induced pressure overload [TG(mREN2)27]. As judged from the depletion of myocardial norepinephrine stores, sympathetic activation was more pronounced in the left than in the right ventricles. In addition, norepinephrine uptake1 carrier sites were reduced in left but unchanged in right ventricles. Gene expression of the carrier was unchanged in stellate ganglia. An increase of Gialpha expression and a heterologous adenylyl cyclase desensitization occurred only in the left but not in the right ventricles, whereas a reduction of beta-adrenergic receptors was observed in both chambers. We concluded that general sympathetic activation can lead to beta-adrenoceptor downregulation but that pressure overload further increases sympathetic activation involving norepinephrine uptake mechanisms in the left ventricles, resulting in heterologous beta-adrenergic desensitization.

Adenylyl Cyclases↗
PubMed1998

PM and D1S80 loci gene frequencies in the Zaragoza population of northern Spain.

LDLR, GYPA, HBGG, D7S8, GC (PM loci) and D1S80 are widely used in forensic casework analyses and population data are required to estimate the frequency of a DNA profile. This paper presents the results of a survey aimed at investigating the allele and genotype frequency distribution of these loci in an important Spanish population (Zaragoza, North Spain). Statistical analysis to determine whether allele frequencies were in Hardy-Weinberg equilibrium was carried out as well as to obtain some parameters of medicolegal interest. There was no evidence of association between the alleles of the loci. The Zaragoza sample does not differ substantially from other Caucasian populations.

Alleles↗