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Biomedical subjects

B Trimarco

Publications and source records attributed to B Trimarco.

At least 55 records · Page 3Linked to original sources
PubMed1997

Insulin enhances endothelial alpha2-adrenergic vasorelaxation by a pertussis toxin mechanism.

To investigate whether insulin effect on endothelium is related to a specific signal transduction pathway or reflects a more generalized action of the hormone, we studied in aortic rings of Wistar-Kyoto (WKY) rats the effects of the hormone on endothelium-dependent relaxations generated by acetylcholine, adenosine diphosphate, the selective alpha2-adrenergic agonist UK 14,304, and the calcium ionophore ionomycin. The responses were evaluated both in control conditions and after 30 minutes of exposure to three different levels of insulin (30, 100, and 500 microU/mL). Insulin failed to modify the phenylephrine aortic contractions and the relaxations induced by acetylcholine, adenosine diphosphate, and ionomycin. In contrast, both 100 and 500 microU/mL insulin were able to potentiate the UK 14,304-induced vasorelaxation (+96+/-19% and +91+/-12%, respectively). Pertussis toxin, which causes alpha2-adrenergic receptor Gi uncoupling, reduced the alpha2-adrenergic vasorelaxation and prevented the insulin potentiation of the response to UK 14,304. Furthermore, in primary cultured aortic endothelial cells from WKY, we evaluated the conversion of [3H]arginine to [3H]citrulline in response to acetylcholine, ionomycin, and UK 14,304, both in control conditions and during insulin exposure. Again, insulin did not affect basal citrulline production or the increase induced by acetylcholine and ionomycin, whereas it potentiated the response to UK 14,304. Finally, in aortic rings of spontaneously hypertensive rats, insulin treatment (100 and 500 microU/mL) was unable to enhance the alpha2-adrenergic vasodilator response; in vascular endothelial cells from spontaneously hypertensive rats, insulin did not potentiate the increase in citrulline production evoked by UK 14,304. In conclusion, insulin selectively enhances alpha2-adrenergic endothelial vasorelaxation through a pertussis toxin-sensitive mechanism, by potentiating endothelial nitric oxide production. This vasorelaxant mechanism is altered in spontaneously hypertensive rats.

Adrenergic alpha-Agonists↗
PubMed1997

Ambulatory monitoring of left ventricular function: walk and bicycle exercise in congestive heart failure.

UNLABELLED: The aim of this study was to assess changes in left ventricular (LV) function during 6-min walk test and cardiopulmonary exercise by continuous radionuclide monitoring in patients with congestive heart failure (CHF). METHODS: Seventeen patients with CHF and 10 normal subjects underwent monitoring of LV function (Vest) during 6-min walk test and during bicycle exercise with combined analysis of pulmonary gas exchange. During cardiopulmonary exercise, all parameters of LV function were measured at rest, at the anaerobic threshold (AT) and at peak oxygen uptake (peak VO2). RESULTS: In the normal subjects, during the walk test, heart rate (HR), ejection fraction (EF), end-diastolic volume (EDV), cardiac output (CO) and stroke volume (SV) significantly increased from rest to peak (all p < 0.001), while end-systolic volume (ESV) significantly decreased from rest to peak (p < 0.001). In patients with CHF, during the walk test, HR, EDV, ESV and CO significantly increased from rest to peak (p < 0.001), EF significantly decreased from rest to peak (p < 0.001) and SV did not show significant change. During cardiopulmonary exercise, normal subjects showed a significant increase in HR and CO, from rest to AT and from AT to the peak VO2 (p < 0.001). EF, EDV and SV significantly increased from rest to AT (p < 0.001), with no significant change from AT to peak VO2. ESV decreased from rest to AT (p < 0.001), showing no significant change from AT to peak VO2. In patients with CHF, HR, CO, ESV and EDV increased significantly from rest to AT (p < 0.001) and from AT to peak VO2 (p < 0.001). EF and SV did not show significant changes from rest to AT, showing a significant decrease from AT to peak VO2 (p < 0.001). CONCLUSION: Vest can be used to evaluate cardiac responses during 6-min walk test and cardiopulmonary exercise in patients with CHF. In such patients, significant impairment of LV function is already present during submaximal physical exercise becoming more evident during the anaerobic phases of bicycle exercise.

Case-Control Studies↗
PubMed1997

Adenosine coronary vasodilation in coronary artery disease: technetium-99m tetrofosmin myocardial tomography versus echocardiography.

UNLABELLED: This study compared the results of adenosine 99mTc-tetrofosmin cardiac tomography with those of adenosine echocardiography in identifying patients with coronary artery disease (CAD) and in localizing individual stenosed, coronary vessels. METHODS: Twenty-six consecutive patients with suspected or known CAD had simultaneous adenosine (140 micrograms/Kg/min intravenously) 99mTc-tetrofosmin tomography and two-dimensional echocardiography. All patients had coronary angiography within 4 wk from imaging studies. Regional 99mTc-tetrofosmin activity was quantitatively measured in 78 coronary vascular territories and echocardiographic left ventricular function was assessed in corresponding regions. RESULTS: At coronary angiography one patient had normal coronary vessels, 12 patients one-vessel and 13 had multivessel disease (> or = 50% luminal stenosis). Among the 25 patients with CAD, 22 showed perfusion defects at adenosine 99mTc-tetrofosmin tomography (sensitivity 88%) and 17 had abnormal echocardiographic study (sensitivity 68%, p < 0.05 versus 99mTc-tetrofosmin). Agreement for the identification of patients with CAD between adenosine 99mTc-tetrofosmin tomography and echocardiography was observed in 21 (81%) of the total 26 patients, with a kappa value of 0.45. Overall sensitivity, specificity and diagnostic accuracy for detection of individual stenosed vessels were 79%, 88% and 83% for 99mTc tetrofosmin and 57%, 68% and 61% (all p < 0.05 versus 99mTc-tetrofosmin) for echocardiography. Concordance between adenosine 99mTc-tetrofosmin tomography and echocardiography in the detection of individual stenosed coronary vessels was observed in 57 (73%) of the 78 vascular territories, with a kappa value of 0.36. CONCLUSION: Adenosine-induced coronary vasodilation associated with quantitative 99mTc-tetrofosmin tomography is more accurate than adenosine echocardiography in identifying patients with CAD and in detecting individual stenosed coronary vessels.

Adenosine↗
PubMed1997

From the monitoring of severe to a survey of mild adverse effects of current antihypertensive therapy: the hidden side of the iceberg. The Scientific Committee of the Italian Pharmacoepidemiology Survey on Antihypertensive Therapy.

One of the most important causes of the unsatisfactory results of antihypertensive therapy in current medical practice is the difficulty in evaluating individual tolerability to the various antihypertensive agents. The methods commonly used, i.e. assessment in controlled studies of limited duration, or notification to pharmacovigilance authorities, clearly underestimate the problem. In order to obtain more correct information on antihypertensive practice, an Italian pharmacoepidemiological study has recently been planned, and the results of a pilot phase of this study are reported here.

Antihypertensive Agents↗
PubMed1997

One-year effect of myocardial revascularization on resting left ventricular function and regional thallium uptake in chronic CAD.

UNLABELLED: It is still unclear whether in patients with chronic coronary artery disease (CAD) the improvements in myocardial perfusion and left ventricular (LV) function induced by revascularization persist in the long run. This study was planned to evaluate the 1-yr effects of successful revascularization on myocardial perfusion and LV function in patients with CAD and to assess the accuracy of thallium imaging in the prediction of functional recovery 1 yr after revascularization. METHODS: Thirty-eight patients with chronic CAD who were revascularized (experimental group) underwent, while off drugs, 201Tl tomography, two-dimensional echocardiography and radionuclide angiography before and after a 1-yr follow-up. Twenty-nine patients with similar characteristics who were not revascularized (control group) and completed the 1-yr follow-up were also studied. Regional thallium activity was quantitatively measured in 13 segments per patient. Systolic function was assessed by echocardiography in corresponding segments. RESULTS: In the experimental group, at baseline, on the basis of regional LV function and thallium uptake, 276 segments were normal, 169 dysfunctional-viable and 49 nonviable. After revascularization, the majority (75%) of the dysfunctional-viable segments at baseline showed functional recovery at follow-up, whereas the majority (81%) of the nonviable segments at baseline did not. Simultaneously, LV ejection fraction increased 4 wk after revascularization (from 39% +/- 9% to 42% +/- 10%, p < 0.01) and remained unchanged after 1-yr (43% +/- 8%, p < 0.01 versus baseline study). LV wall-motion score index after 1 yr was reduced (from 1.68 +/- 0.4 to 1.42 +/- 0.3, p < 0.001) as compared with baseline. On the contrary, in the control group, no change in myocardial perfusion and LV function was detected after the 1-yr follow-up. CONCLUSION: In patients with chronic CAD, successful coronary revascularization induces a stable improvement in myocardial perfusion and LV function, which is still detectable after a 1-yr follow-up. Furthermore, preserved thallium uptake in dysfunctional regions is predictive of functional recovery after revascularization.

Angioplasty, Balloon, Coronary↗
PubMed1996

Association and cosegregation of stroke with impaired endothelium-dependent vasorelaxation in stroke prone, spontaneously hypertensive rats.

While hypertension is a major risk factor for stroke, it is not its sole determinant. Despite similar blood pressures, spontaneously hypertensive rats (SHR) do not share the predisposition to cerebrovascular disease typical of stroke-prone spontaneously hypertensive rats (SHRSP). We investigated vascular function in male SHR and SHRSP as well as in SHRSP/SHR-F2 hybrid animals. Animals were maintained on the appropriate dietary regimen necessary for the manifestation of stroke. Among the hybrid animals, a group of stroke-prone and a group of stroke-resistant rats were selected. Blood pressure was similar in all groups. Endothelium-independent vascular reactivity tested on isolated rings of thoracic aorta and basilar artery after death showed similar contractile and dilatory responses to serotonin and nitroglycerin, respectively, in all groups. In contrast, endothelium-dependent relaxation, in response to acetylcholine or substance P, was markedly reduced in SHRSP compared with SHR. Similarly, reduced vasodilatory responses were present in aortae of F2 rats that had suffered a stroke when compared with SHR or F2 rats resistant to stroke. The observed association and cosegregation of stroke with significant and specific impairment of endothelium-dependent vasorelaxation among SHRSP and stroke-prone F2 hybrids, respectively, suggest a potential causal role of altered endothelium-dependent vascular relaxation in the pathogenesis of stroke.

Acetylcholine↗
PubMed1996

Insulin modulation of beta-adrenergic vasodilator pathway in human forearm.

BACKGROUND: Insulin modulates sympathetic vasoconstriction, but the mechanisms underlying this effect are not completely elucidated. We have recently investigated the insulin effect on the alpha 1- and alpha 2-adrenergic vasoconstriction pathway, where it is still conflicting with the possible insulin influence on the beta-adrenergic vasodilator pathway. The aim of the present study was to investigate this issue. METHODS AND RESULTS: The study was performed on the forearm of healthy humans, and all test substances were infused into the brachial artery at systemically ineffective rates. In five subjects, we evaluated isoproterenol-induced vasodilation (1, 3, 6, and 9 ng. kg-1. min-1) both under control conditions and during insulin infusion (0.05 mU. kg-1. min-1). In another group of five subjects, we tested whether the vasorelaxant effect of sodium nitroprusside (1, 2, 4, and 8 ng . kg-1 . min-1) was modified by insulin. Moreover, to explore whether the interaction between insulin and forearm beta-adrenergic pathway participates in insulin modulation of sympathetic-evoked vasoconstriction, we measured in six normal subjects the forearm vascular response to lower-body negative pressure under control conditions and during intrabrachial infusion of insulin alone and in combination with a selective beta-adrenergic blocking agent (propranolol 10 micrograms/100 mL per minute). Finally, to verify whether insulin interaction with the beta-adrenergic pathway may also account for insulin modulation of alpha 2-adrenergic vasoconstriction, we assessed the vascular response to a selective alpha 2-adrenergic agonist before and after propranolol administration. Insulin exposure potentiated the vascular responsiveness to isoproterenol but did not affect the vasodilator response to sodium nitroprusside. Furthermore, the insulin-induced attenuation of sympathetic vasoconstriction was partially corrected by propranolol. In contrast, the insulin modulation of alpha 2-adrenergic vasoconstriction was not influenced by beta-adrenergic blockade. CONCLUSIONS: Taken together, our results suggest that insulin modulation of sympathetic-induced vasoconstriction is carried out through an interaction of the hormone with the pathways of both alpha 2-and beta -adrenergic receptors.

Adrenergic beta-Antagonists↗
PubMed1996

Influence of digitalis on left ventricular functional response to exercise in congestive heart failure.

This was a double-blind, placebo-controlled, crossover study designed to determine the influence of digitalis treatment on left ventricular (LV) response to physical exercise in patients with congestive heart failure (CHF). In 10 patients with CHF (ejection fraction 29 +/- 2%), LV function was assessed during upright bicycle exercise using an ambulatory radionuclide detector for continuous noninvasive monitoring of cardiac function. Exercise was performed during control conditions and after a 3-week treatment with digoxin (0.25 mg/day orally) or placebo. Ten normal volunteers matched for sex and age constituted the control group. In normals, exercise ejection fraction and end-diastolic volume increased (both p <0.001), while end-systolic volume decreased progressively (p <0.001). In control conditions, patients with CHF had a sharp increase in heart rate during exercise, while ejection fraction did not change; both end-diastolic and end-systolic volumes increased significantly (both p <0.001) during exercise. During digoxin treatment, heart rate response to exercise recorded in patients with CHF was comparable to that recorded in normal subjects. In addition, a significant increase in ejection fraction during exercise was detected (P <0.001), and the increase in end-systolic volume was significantly smaller than that observed in control conditions (p <0.05). When patients received placebo, the responses of LV function to exercise were comparable to those observed in control conditions. These findings demonstrate that digitalis has a favorable influence on LV functional adaptation to exercise in CHF.

Adult↗
PubMed1996

Adaptive changes in the acute haemodynamic effects of cilazapril during chronic treatment. Comparison with long-term clinical effect.

OBJECTIVE: To study the adaptive changes in the acute haemodynamic response to ACE inhibition during chronic treatment in CHF. METHODS: The acute and chronic effects of oral cilazapril (CLZ) treatment, an ACE-inhibitor with prolonged duration on haemodynamic measures (PCWP, PAP, RAP, CI and SVR) and clinical parameters (Quality-of-Life and NYHA class) were investigated in a double-blind, randomised, placebo-controlled trial in CHF. One hundred and thirty five patients (112 completing) in NYHA Classes II-III, on digitalis and diuretic treatment, were randomised after 2 weeks of placebo run-in, to receive either placebo or CLZ 0.5 mg, 1.0 mg or 2.5 mg daily for 12 weeks, followed by 2 week placebo wash-out. Haemodynamic studies, including exercise tests before and 3 h after medication, were performed on the first and last days of treatment. Measurements were performed at rest and at the maximum exercise level. RESULTS: In ACEI-naive patients oral CLZ 0.5 and 1 mg/d caused a dose dependent decrease in PCWP and diastolic PAP, and a significant reduction of SVR mg. A slight increase in CI was observed in all groups. The maximum effect was observed 3-5 h post dose. After 12 weeks of oral treatment, the acute response was similar but was attenuated relative to the first dose. Exercise tolerance improved in a dose dependent manner. The NYHA classification remained unchanged or improved in the majority of patients. Entry into the 2.5 mg group had to be terminated at an early stage due to severe adverse events observed after the first dose. CONCLUSION: During chronic treatment, the haemodynamic response to oral cilazapril was attenuated, indicating that continued clinical improvement in patients with CHF on CLZ is independent of to its acute haemodynamic effects.

Adult↗
PubMed1996

Effects of tissue factor induced by oxygen free radicals on coronary flow during reperfusion.

Tissue factor is a transmembrane protein that activates the extrinsic coagulation pathway by binding factor VII. Endothelial cells, being in contact with circulating blood, do not normally express tissue factor. Here we provide evidence that oxygen free radicals induce tissue factor messenger RNA transcription and expression of tissue factor procoagulant activity in endothelial cells in culture. Isolated, perfused rabbit hearts exposed to exogenous oxygen free radicals also showed a marked increase in tissue factor activity within the coronary circulation. Furthermore, in ex vivo and in vivo hearts subjected to ischemia and reperfusion, a condition associated with a production of oxygen free radicals in large amounts, a marked increase in tissue factor activity occurred. This phenomenon could be abolished by oxygen radical scavengers. This increase in tissue factor activity during postischemic reperfusion was accompanied by a significant decrease in coronary flow, suggesting that increase in tissue factor activity with the consequent activation of the coagulation cascade might impair coronary flow during reperfusion and possibly contribute to the occurrence of reperfusion injury.

Animals↗
PubMed1996

[Computerized tomography with single photon emission (SPECT) with technetium-99m MIBI (99mTc-MIBI) in the identification of viable myocardium in patients with chronic ischemic cardiopathy and left ventricular dysfunction].

Resting 99mTc-MIBI cardiac imaging may be poorly accurate in identifying the presence of viable myocardium in patients with chronic coronary artery disease (CAD). In this study, we directly compared the results of resting 99mTc-MIBI SPECT with initial (1 hr) and delayed (5 hrs) images with those of 99mTc-MIBI SPECT after nitroglycerine (NTG) administration in 31 patients with chronic CAD. All patients also underwent rest-redistribution thallium-201 (201Tl) SPECT. In 8 patients, echocardiography was performed before and after coronary revascularization (Rev). Of 682 myocardial segments, 197 showed a marked reduction (< 50% of peak) in MIBI uptake on initial images. MIBI uptake (> or = 10%) was increased in 47 (24%) segments on delayed images (from 43 +/- 8% to 60 +/- 8%, p < 0.001) and in 54 (27%) segments after NTG (from 42 +/- 8% to 60 +/- 8%, p < 0.001). The results of delayed and NTG MIBI images were in agreement in most segments (n = 160, 81%). The results of delayed and NTG MIBI images were in disagreement in the remaining 37 (19%) segments. In particular, 15 segments showed reversible defects on delayed, but not on NTG MIBI images, while 22 on NTG, but not on delayed MIBI images. All the segments with reversible MIBI defects on delayed and/or NTG images were identified as viable on TI-201. In the 8 pts examined before and after Rev. 83% of segments with reversible MIBI defects on delayed images and 87% of those with reversible defects after NTG showed functional recovery after Rev; furthermore, in these patients a significant improvement in global left ventricular function was observed after Rev, as shown by ejection fraction values (from 42 +/- 7% to 47 +/- 7%, p < 0.01). These comparative results show that resting delayed and NTG MIBI imaging provide similar information to identify viable myocardium and to predict functional recovery after coronary Rev in chronic CAD.

Adult↗
PubMed1996

The crosstalk between insulin and the sympathetic nervous system: possible implications in the pathogenesis of essential hypertension.

Patients with non-insulin dependent diabetes mellitus and obesity show an elevated risk for development of arterial hypertension, while many non-obese, non-diabetic patients with essential hypertension display resistance to insulin-induced glucose disposal, accompanied by hyperinsulinaemia. This close association has lead some investigators to postulate that insulin resistance could be implicated in the pathogenesis of essential hypertension. Among the various factors considered as potential links between insulin resistance and high blood pressure, the sympathetic nervous system can be considered a prime candidate. In particular, our recent data in hypertensive patients have documented that the muscle sympathetic response evoked by insulin is about threefold greater than that observed in normal subjects. Such finding is well in agreement with previous observations in hypertensives obtained with experimental maneuvers and extends them by showing an abnormal sympathetic response to a physiological stimulus like insulin, so important in every day life. Recent data both from our and other laboratories have clearly established that an acute activation of sympathetic nervous system is able to antagonize insulin-mediated glucose uptake in the skeletal muscle, making very real the possibility that a primary defect in insulin sensitivity in hypertension may be further aggravated by the greater sympathetic response evoked by episodic stimuli, such as postprandial hyperinsulinaemia. However, while insulin evokes an increase in sympathetic nervous activity, at same time it is able to blunt the vasoconstrictive effects caused by the reflex sympathetic activation. Such vascular modulating effect of insulin is lost in essential hypertension, indicating that the resistance to insulin effect in this disease is not only present in skeletal muscle metabolism but it is also evident at the vascular level.

Blood Glucose↗
PubMed1995

Radionuclide monitoring of cardiac adaptations to volume loading in patients with dilated cardiomyopathy and mild heart failure. Effects of angiotensin-converting enzyme inhibition.

BACKGROUND: Cardiac adaptations to volume overload have been poorly investigated in heart failure. The aim of this study was to assess dynamic left ventricular responses to acute volume loading by continuous radionuclide monitoring in patients with asymptomatic to mildly symptomatic left ventricular dysfunction. METHODS AND RESULTS: Left ventricular end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), and peak filling rate (PFR) were monitored by a radionuclide detector (Vest) before and during volume expansion (sodium chloride, 0.9%, 0.25 mL.kg-1.min-1 for 2 hours) in 10 patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (New York Heart Association class I or II, ejection fraction < 50%). The patients were studied off treatment and after 6 to 8 weeks of oral treatment with enalapril (5 mg/d). A control group of 11 age- and sex-matched healthy volunteers (N group) was also studied. In the N group, volume loading caused prompt and sustained increases of EDV, EF, and PFR (all P < .001), whereas ESV was progressively reduced (P < .001), and heart rate and blood pressure did not change. In contrast, in DCM, EDV showed a smaller increase than in the N group (two-way ANOVA: F = 5.98, P < .001), ESV increased (P < .001), and EF and PFR remained unchanged. After enalapril, the cardiac adaptations to volume loading were restored to normal. In particular, EDV, EF, and PFR increased (P < .001), and ESV was reduced (P < .001). In 6 additional DCM patients studied before and after 6 to 8 weeks of placebo treatment, left ventricular responses to volume loading remained unchanged. CONCLUSIONS: Left ventricular dynamic adaptations to acute volume loading are compromised in patients with idiopathic DCM and mild heart failure. These impaired responses are ameliorated by treatment with enalapril.

Adult↗
PubMed1995

Efficacy and safety of the 200-300 mg sustained release formulation of diltiazem administered once daily in patients with stable angina.

The aim of this multicentre randomised double blind study was to compare the efficacy and safety of the 200-300 mg sustained release diltiazem formulation administered once daily (200-300 SR) with standard diltiazem (D) given three or four times daily to patients with stable angina. Patients aged 59 years, with a reproducible exercise test on placebo, were randomised to 4 weeks of treatment with 200-300 SR (n = 70) or D (n = 74). The initial dosage was 200 mg in the 200-300 SR group and 60 mg t.i.d. in the D group, increased to 300 mg once daily or 60 mg q.i.d., respectively, if ergometric parameters, which were always measured at the end of the dosing period, had not improved after two weeks. After 4 weeks of treatment, the antianginal efficacy at rest was comparable in the 200-300 SR and the D group; there was a prolongation of the total duration of exertion of 14% and 18% respectively (P < 0.01 vs placebo for both groups with no intergroup difference). A dose-effect relation was found with both formulations. The 200-300 SR formulation gave full 24 hour anti-ischaemic protection when administered once daily. Its efficacy and safety were comparable to those of standard diltiazem t.i.d. or q.i.d. in patients with stable angina. The once daily administration should improve treatment compliance.

Adult↗
PubMed1995

Regulation of 11 beta-hydroxylase cytochrome p450 expression by cholesterol in spontaneously hypertensive rats.

OBJECTIVE: To investigate whether hypercholesterolaemia interferes with the expression of the enzymes involved in steroid biosynthesis in the adrenal cortex. METHODS: Twenty-four 5-week-old male spontaneously hypertensive rats (SHR) were randomly assigned to a high (1%) cholesterol diet (n = 8) or to a matched cholesterol-free diet (n = 8) for 6 weeks. A third group (n = 8) was studied after 2 weeks of washout from the high-cholesterol intake. A cohort of age- and sex-matched normotensive Wistar-Kyoto (WKY) rats (n = 24) underwent the same treatments and was used as a control. RESULTS: In SHR cholesterol feeding reduced urinary sodium excretion (0.8 +/- 0.1 versus 1.4 +/- 0.1 mmol/24 h in the cholesterol-free group), increased plasma aldosterone levels (299 +/- 60 versus 154 +/- 24) and reduced plasma corticosterone levels (142 +/- 21 versus 278 +/- 35 ng/ml). Those responses were associated with a reduction of 11 beta-hydroxylase cytochrome P450 messenger RNA (mRNA) in the adrenal cortex (-52.3 +/- 3.4%) whereas aldosterone synthase mRNA remained unchanged. That effect and the changes in electrolyte excretion and steroid levels were no longer detectable after withdrawal of the diet. In WKY rats high-cholesterol diet induced no significant changes in urinary electrolyte excretion, steroid levels and expression of 11 beta-hydroxylase cytochrome P450 and aldosterone synthase in the adrenals. CONCLUSIONS: The present results indicate that in SHR hypercholesterolaemia selectively interferes with the adrenal steroid biosynthetic pathway by reducing the expression of 11 beta-hydroxylase, leading to accumulation of mineralocorticoids and sodium retention.

Adrenal Cortex↗
PubMed1995

Insulin modulation of vascular reactivity is already impaired in prehypertensive spontaneously hypertensive rats.

Hyperinsulinemia reduces the vasoconstrictive response to norepinephrine in Wistar-Kyoto rats (WKY) but not in spontaneously hypertensive rats (SHR). It has been hypothesized that this difference in the vascular effect of insulin could be a hallmark of the hypertensive state. To test this hypothesis we studied SHR before (5 weeks old, n = 10) and after (15 weeks old, n = 10) the establishment of hypertension as well as two groups of age- and sex-matched WKY (5 weeks old, n = 14; 15 weeks old, n = 13). Blood pressure was significantly higher in SHR compared with WKY (181 +/- 5 versus 118 +/- 6 mm Hg, respectively, P < .001) in the 15-week-old rats but not in the 5-week-old rats (121 +/- 5 versus 117 +/- 3 mm Hg, P < NS). We tested vascular reactivity using increasing amounts of norepinephrine (from 10(-10) to 10(-5) mmol/L) on isolated aortic rings in control conditions and after 30 minutes of exposure to 715 pmol/L insulin. In WKY insulin reduced the vascular response to norepinephrine in both the 5-week-old (repeated-measures ANOVA with grouping factor: F = 2.443, P < .05) and 15-week-old (F = 9.667, P < .01) groups. In SHR at both ages insulin failed to modify the vascular response to norepinephrine (5 weeks: F = 0.107, P < NS; 15 weeks: F = 0.075, P < NS). Sodium nitroprusside was able to attenuate the vascular response to norepinephrine in WKY and SHR at 5 and 15 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗