Search PubMed⌕ Search

Biomedical subjects

R C Tarazi

Publications and source records attributed to R C Tarazi.

At least 19 recordsLinked to original sources
PubMed1990

Effects of antihypertensive drugs on heart and resistance vessels.

STUDY OBJECTIVE - The aim of the study was to examine the effects of antihypertensive drugs on heart and resistance vessels to see whether regression of peripheral vascular hypertrophy accompanies reduction in cardiac mass. DESIGN - Matched groups of spontaneously hypertensive and control rats were treated for 12 weeks with captopril (average dose 65 mg.kg-1.d-1) or hydrochlorothiazide (73 mg.kg-1.d-1) and compared to untreated groups. Perfusion pressure, which has been validated as an index of hypertrophy of resistance vessels, was determined in hind limbs of pithed rats at constant blood flow and maximum vasodilatation. SUBJECTS - Experimental animals were 14 week old male spontaneously hypertensive (SHR) rats (n = 41) and strictly age matched Wistar Kyoto rats (n = 12). SHR rats were assigned at random to three groups: (a) captopril treated (n = 15), (b) hydrochlorothiazide treated (n = 15), (c) control (n = 11). MEASUREMENTS and RESULTS - Mean perfusion pressure was 29.5(SEM 0.4) mm Hg in untreated Wistar Kyoto rats and 37.4(0.5) mm Hg in untreated SHR rats. In comparison with untreated SHR rats, treatment with captopril lowered blood pressure, perfusion pressure [35.2(0.3) v 37.4(0.5) mm Hg, p less than 0.01)], and left ventricular to body weight ratio [2.28(0.03) v 2.63(0.05) mg.g-1, p less than 0.01)]. Treatment with hydrochlorothiazide also lowered blood pressure but had no significant effect on left ventricular weight to body weight ratio [2.54(0.04)]. However, perfusion pressure was reduced to 35.3(0.5) mm Hg, p less than 0.01. CONCLUSIONS - For equal regression of vascular hypertrophy, captopril and hydrochlorothiazide had different effects on regression of left ventricular hypertrophy. Thus left ventricular and vascular structural changes may respond differently to the same drug in the same animal.

Animals↗
PubMed1988

Norepinephrine-induced enlargement of nucleus in cultured myocardial cells.

The change in the nuclear size of neonatal rat myocardial cells was evaluated under the culture conditions of exposure to norepinephrine (NE). Daily administration for 1 week of 0.2, 2, and 20 ng/ml NE induced a significant increase in nuclear size as a result of the dose-dependent quality of the nuclei. NE also stimulated a beating response in the cultured myocardial cells because of this dose dependency. A good correlation was found between the two markers and the NE dose dependency. Single or mononucleated myocardial cells often appeared in the NE-treated groups. Ornithine decarboxylase activity was not acutely stimulated even by 20 ng/ml NE. These observations suggest that administration of NE induces nuclear enlargement and enhances nuclear function through the stimulation of beating. Further, there may not be a direct relation between nuclear enlargement and the polyamine synthesis pathways.

Animals↗
PubMed1988

Clinical implications of primary aldosteronism with resistant hypertension.

Twenty-eight patients with resistant hypertension were found to have primary aldosteronism; 25 had solitary adenoma and 3 had adrenal hyperplasia. All were severely hypertensive despite receiving three or more antihypertensive agents, including conventional doses of diuretics, sympatholytics, and vasodilators. Hypervolemia (24 patients) or normovolemia (2 patients) despite severe diastolic hypertension was the hallmark in 26 patients. Adequate salt and water depletion alone with spironolactone (200 mg/day) and hydrochlorothiazide (50-100 ng/day) reduced arterial pressure in all. Twenty-two patients had surgical removal of a solitary adenoma. Over 1 to 2 years of follow-up, 13 were normotensive without medication, and six required hydrochlorothiazide and three hydrochlorothiazide plus a beta-blocker to normalize blood pressure. Blood pressure response to surgery had no relation to either duration or severity of hypertension. Six patients (three with hyperplasia, three with adenoma) have continued diuretic therapy and are normokalemic and normotensive. These results indicate that primary aldosteronism can be associated with sever and drug-resistant hypertension, that maintained hypervolemia is the reason for resistance to therapy, that sustained volume depletion is the most important therapeutic goal for these patients, and that cure can be achieved despite prolonged and severe hypertension.

Adenoma↗
PubMed1987

Hemodilution affects the pressor response to norepinephrine.

A hindlimb preparation of 19 male rats was used to determine the responses to norepinephrine (NE) at different levels of hemodilution at a constant flow, at increased flow and maintained pressure, and after reversal of hemodilution. An initial series demonstrated that the preparation remained stable with unchanged blood pressure, plasma electrolytes, and blood gases; and had reproducible responses to NE throughout the experiment. Two levels of isovolumic hemodilution were achieved by blood/hetastarch exchanges equivalent to 1.5% and 3.0% body weight, which reduced hematocrit to 30.8 +/- 2% and 18.7 +/- 1.5%, respectively. Hemodilution reduced the perfusion pressure from 73.6 mmHg to 58.6 and 55.7 mmHg following 1.5% and 3.0% hemodilution, respectively. A dose-response relationship to NE (0.1, 0.3, 1.0 micrograms/kg) was obtained. The responses to NE were markedly reduced following both 1.5% and 3.0% hemodilution. Retransfusion of packed red blood cells increased the hematocrit from 21.1 +/- 2.2% during hemodilution to 41.2 +/- 2.1% (P less than .01). Concomitantly, perfusion pressure increased from 46.2 +/- 3.6 to 68.3 +/- 6.5 mmHg (P less than .001), close to prehemodilution levels (65.3 +/- 5.3 mmHg). Restoration of hematocrit levels restored responses to NE. In a third series, hemodilution was continued, but the blood flow was increased from 4.0 to 8.3 +/- 0.9 mL/min, and perfusion pressure returned to baseline values. This also restored the pressor responsiveness to NE to near normal.

Animals↗
PubMed1987

Localization of autonomic nervous system dysfunction in dialysis patients.

Autonomic nervous system dysfunction has been described frequently in uremic patients. The purpose of this study is to determine the localization of this abnormality and to study the possible relationship between autonomic dysfunction and the occurrence of dialysis hypotension. Sixteen consecutive patients participated in the study, 5 of whom had a history of dialysis-induced hypotension. These 5 patients were compared to the other 11 as regards the cardiovascular response to isoproterenol infusion, tilt test and arteriovenous (AV) fistula occlusion. None of the responses to the above mentioned stimuli was significantly different between the 2 groups. In the whole study population, an index of parasympathetic control of heart rate (variation of heart period, VHP) was reduced (31 +/- 5 vs. 59 +/- 9 ms in age-matched controls; p less than 0.025). Heart rate and diastolic blood pressure response to isoproterenol infusion was normal (+23 +/- 2 beats/min and -9 +/- 3 mm Hg; p less than 0.005 for both), indicating normal response of effector organs to beta-adrenergic agonist stimulation. Similarly, plasma norepinephrine increased significantly (+294 +/- 51 pg/ml; p = NS from normal laboratory values) in response to head-up tilt, and heart rate increased simultaneously in all but 5 patients. Blood pressure response was within normal after 10 min of head-up tilt at 60 degrees in all but 3 patients; only 1 of these 3 patients was in the group of dialysis hypotension. However, during AV fistula occlusion, heart rate did not change markedly, despite the significant increase in systolic blood pressure, suggesting an altered sensitivity of baroreceptor reflex arc.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Differential structural responses of small resistance vessels to antihypertensive therapy.

Regression of left ventricular hypertrophy after control of blood pressure has been documented with some antihypertensive agents but not with others. To determine whether similar differences in regression of wall thickening also occur in resistance vessels during treatment, matched groups of spontaneously hypertensive rats (SHR) were treated for 12 weeks with either hydralazine (H) or captopril and hydrochlorothiazide (C-D) and they were compared with untreated SHR and Wistar-Kyoto rats (WKY). Perfusion pressure was then determined in the hindlimbs of pithed rats under conditions of constant blood flow (4.0 ml/min) and maximal vasodilation (hemodilution to 22% hematocrit combined with continuous nitroprusside and papaverine infusion). This perfusion pressure, which has been validated as an index of thickening (hypertrophy) of resistance vessels walls, averaged 26.8 +/- 0.4(SE) mm Hg in untreated WKY (n = 12) and 37.6 +/- 0.4 mm Hg in untreated SHR (n = 11) (p less than .01). Treatment with H or C-D controlled blood pressure equally in SHR, but the two drugs had significantly different effects on both left ventricular hypertrophy and resistance vessels. Perfusion pressure was reduced from 37.6 +/- 0.4 mm Hg to 34.0 +/- 0.5 mm Hg (p less than .01) with C-D but only to 36.5 +/- 0.5 mm Hg with H (NS). Left ventricular weight was significantly reduced by C-D (2.02 +/- 0.02 vs 2.63 +/- 0.05 mg/g, p less than .01) but only to 2.44 +/- 0.05 mg/g by H.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of chronic exercise on the coronary circulation in conscious rats with renovascular hypertension.

Since various studies suggest that chronic physical conditioning promotes myocardial vascularity, we investigated whether it could prevent the coronary reserve abnormalities of hypertensive cardiac hypertrophy. One week after operation, female Sprague-Dawley rats with two-kidney, one clip Goldblatt hypertension were either subjected to a moderate exercise program by swimming (n = 21) or kept sedentary (n = 16) for 9 weeks. Sedentary (n = 16) and exercised (n = 15) sham-operated rats served as controls. Maximal coronary blood flow and minimal coronary resistance, either per unit mass or for the entire left ventricle, an index of the functional cross-sectional area of the coronary resistance vessels, were determined in conscious, unrestrained rats by left atrial microsphere injection following maximal vasodilation with carbochrome (12 mg/kg). Following exercise, left ventricular mass was moderately (+5-10%) but significantly increased in normotensive rats, whereas left ventricular hypertrophy was significantly accentuated in the hypertensive rats. Minimal coronary resistance for the entire left ventricle was significantly decreased (-24%) in normotensive rats but did not change significantly in hypertensive rats. Minimal coronary resistance per unit mass (the coronary vasodilator reserve) tended to decrease in normotensive rats (-17%), whereas it tended to be further augmented in hypertensive rats (+13%). However, these differences were marginally significant and were not associated with any changes in maximal coronary blood flow per unit mass (the coronary flow reserve). Thus, in normal rats, exercise promoted myocardial arterial vascularity in parallel with the development of cardiac hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The chronic effect of nitrendipine on heart and regional blood flow in renovascular hypertensive rats.

Nitrendipine, a new calcium entry blocker, was administered to renovascular hypertensive rats (2K1C Goldblatt) (RHR, n = 8) and sham operated control rats (ShC, n = 8) to evaluate the effects on left ventricular hypertrophy and regional blood flow using radioactive microspheres. Nine untreated RHR and 8 untreated ShC served as control groups. After 6 weeks treatment (20 mg/kg subcutaneously, every other day), blood pressure reduced significantly in both RHR and ShC associated with a reduction in total peripheral resistance. Significant reversal of left ventricular hypertrophy was noted in RHR (1278 +/- 41 to 1024 +/- 19 mg, p less than 0.01), but not in ShC. There was a significant relationship between blood pressure and left ventricular mass in both untreated rats (r = 0.955, p less than 0.001) and treated rats (r = 0.729, p less than 0.005). Nitrendipine increased coronary blood flow in RHR (430 +/- 30 to 566 +/- 47 ml/m/100g, p less than 0.05) as well as in ShC (375 +/- 15 to 508 +/- 29 ml/ml/100g, p less than 0.05), without increasing cardiac oxygen demand. Renal blood flow was unchanged, whereas cerebral blood flow was significantly increased in both RHR (128 +/- 6 to 164 +/- 13 ml/m/100g, p less than 0.01) and ShC (124 +/- 7 to 173 +/- 5 ml/m/100g, p less than 0.01). Thus, long treatment of nitrendipine effectively regressed cardiac hypertrophy toward normal. Nitrendipine reduced total peripheral resistance; however, the effects on regional blood flow were not uniform among various organs.

Animals↗
PubMed1987

Is reversal of cardiac hypertrophy a desirable goal of antihypertensive therapy?

Over the past several years, a growing body of information has confirmed and extended our initial concept that nonhemodynamic as well as hemodynamic factors are responsible for the development of left ventricular hypertrophy in hypertension. We reported the dissociation of these factors in the regression of left ventricular mass and hypertrophy with antihypertensive therapy. Several lines of clinical and experimental studies have been pursued to determine whether cardiac performance, myocardial contractility, and reserve are normal with regression of ventricular mass with treatment. Too few studies have been conducted in vivo, and in the conscious state, and at pretreatment pressures to conclude at this time that normal cardiac function and performance is restored or maintained. Until such data are available, we must conclude that although left ventricular hypertrophy confers a risk, in and of itself, to cardiovascular morbidity and mortality, we do not know whether pharmacologic reversal of cardiac hypertrophy is a desirable therapeutic goal. Several years ago we were convinced that a new and impressive body of information emanating mostly from our laboratories strongly indicated a new concept previously unexpressed by others. We suggested that increasing ventricular mass in hypertension (i.e., left ventricular hypertrophy), although dependent in part on arterial pressure and other hemodynamic factors, was also dependent on participation of a number of "nonhemodynamic" mechanisms. Our early findings, supported by associated reports, suggested that in addition to left ventricular afterload, factors including other pressor mechanisms (e.g., adrenergic function and norepinephrine levels, humoral substances, the renopressor system), aging, race, gender, coexisting diseases, pharmacologic agents, and others may also participate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Converting-enzyme inhibition and coronary blood flow.

The effects of converting-enzyme inhibition (25 mg oral captopril) on coronary hemodynamics in the presence and absence of activation of the renin-angiotension system were studied in 10 patients with mild essential hypertension with no evidence of ischemic heart disease. Coronary blood flow was determined by thermodilution before and after 1 week of diuretic therapy in six patients and before and after placebo in four patients. The diuretic (50 mg/day furosemide) reduced coronary blood flow and increased coronary vascular resistance; in these same patients, captopril reduced mean arterial pressure and the rate-pressure product but increased coronary flow significantly. There was no change in any of these variables after captopril in the placebo group. Similar results were obtained in normotensive rats treated with hydrochlorothiazide; the increase in coronary flow after captopril correlated significantly with the control plasma renin activity. These results in hypertensive humans and normotensive experimental animals indicate that diuretic therapy reduces coronary blood flow significantly, and angiotensin can play a significant role in modulating coronary vascular resistance under conditions associated with activation of the renin-angiotensin system.

Adult↗
PubMed1986

Current therapy, present limitations and future goals for systemic hypertension.

During the past 2 decades, encouraging strides have been made in the recognition and treatment of patients with high blood pressure and in the development of antihypertensive therapy. Concerns surrounding the control of hypertension, however, continue to emerge. As many as two-thirds of hypertensive patients in the US remain inadequately controlled. Although overall cardiovascular mortality has declined since the mid- 1960s, a significant impact of antihypertensive therapy on coronary artery disease morbidity and mortality has not been conclusively demonstrated. Unfavorable metabolic effects associated with traditional step-care antihypertensive therapy with diuretics and beta blockers are increasingly implicated for failure to demonstrate a decrease in coronary artery disease. The availability of newer efficacious antihypertensive therapy that does not adversely affect metabolic parameters is resulting in a reappraisal of traditional step-care. Of particular interest are the calcium channel blockers, because they are efficacious, well tolerated and offer favorable metabolic and hemodynamic profiles. Nitrendipine is a new long-acting member of the 1,4 dihydropyridine class of calcium channel blockers that has shown encouraging results for treatment of hypertension.

Antihypertensive Agents↗
PubMed1986

Nitrendipine, a calcium-entry blocker. Renal and humoral effects in human arterial hypertension.

Thirteen patients with hypertension and normal renal function received nitrendipine, a calcium entry blocker. Nitrendipine did not modify renal blood flow (RBF) or glomerular filtration rate (GFR), decreased mean arterial pressure (MAP) and total peripheral resistance, and did not significantly change cardiac output. Individual RBF changes did not correlate with MAP or cardiac output modifications. Mean arterial pressure changes were inversely correlated with basal renin levels and directly associated with age. Plasma catecholamines and plasma renin activity increased, but plasma aldosterone and plasma volume did not change significantly. However, the greater decrements of MAP tended to be associated with the greater increases in plasma volume. Data show that long-term calcium entry blockade by nitrendipine does not modify RBF or GFR despite the decreased renal perfusion pressure. Further, nitrendipine may be more effective in older patients and the presence of low renin.

Adult↗
PubMed1986

Excessive sodium retention as a characteristic of salt-sensitive hypertension.

To investigate the possibility that salt-sensitive hypertensives have deficient sodium excretion, the sodium retained by 20 hypertensive patients during a salt load (SL = 3.88 mEq/Kg/day) was calculated for 3 days immediately after 4 days of sodium deprivation (SD = 9 mEq/d). Patients were divided into two groups by arterial pressure responses to SD: responders (N = 10) whose pressures became normal rapidly and averaged less than 140/90 during SD and nonresponders (n = 10) whose pressures were not affected. Sodium retention (mEq/Kg) during SL was calculated as cumulative sodium intake minus cumulative urinary sodium divided by body weight. Responders retained more sodium during SL than nonresponders (3.71 +/- 0.96 [SD] vs. 2.52 +/- 1.05 mEq/Kg, p less than 0.02). This could not be explained by a measurable decrease in filtered sodium load since creatinine clearance was the same in each group. Neither was it associated with differences in plasma renin activity (PRA) or aldosterone excretion rates (AER). Whereas PRA was significantly lower in responders at the end of SD, AER was not different; with SL, group values were equally suppressed. Also sodium excretion was not correlated with arterial pressure except in non-responders on the last day of SL. These data indicate that salt-sensitive hypertensives handle sodium differently than nonsalt-sensitive hypertensives.

Adult↗
PubMed1986

Restoration of cardiac function and structure by converting enzyme inhibition possibilities and limitations of long-term treatment in hypertension and heart failure.

There is no doubt that cardiac function can be restored to a great degree in congestive heart failure treated with converting-enzyme inhibitors, but the mechanism of improvement involves the correction of peripheral abnormalities rather than a direct cardiac effect of the drug. There is some evidence that deterioration of cardiac function and progressive cardiac dilation following myocardial infarction can be prevented by treatment with converting-enzyme inhibitors. Regression of left ventricular hypertrophy (LVH) has been obtained by converting-enzyme inhibitors, both in man and in experimental animals. In animal studies, this regression of LVH was associated with restoration of contractile reserve and of coronary flow reserve to normal. The final significance of this restoration of structure and its functional aspects still needs further studies.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Idiopathic hypovolemia.

Eleven patients with orthostatic intolerance had, for no detectable reason, a marked reduction in blood volume (73 +/- 2.29% [SE] of normal). Head-up tilt caused a pronounced increase in heart rate (+ 39 +/- 6 beats/min); one patient had a vasovagal episode after the initial tachycardia. Extensive diagnostic study excluded pheochromocytoma, hypoaldosteronism, or any obvious cause for hypovolemia (total plasma catecholamines, 372 +/- 53 ng/L; plasma aldosterone level, 14.5 +/- 2.56 ng/100 mL; plasma cortisol level, 18.5 +/- 2.4 ng/100 mL). The supine hemodynamic pattern (decreased cardiac output and increased total peripheral resistance with normal ejection fraction and mean transit time) was markedly different from that of hyperbeta adrenergic states. Acute plasma volume expansion (+ 11 +/- 2%) in ten patients using human serum albumin improved both their symptoms and heart rate response to tilt. After long-term blood volume expansion with florinef (E.R. Squibb, Princeton, New Jersey), 0.1 mg twice a day, and a high-salt diet, the head-up tilt test was repeated in five patients. The response was normal in four patients. These observations outline a syndrome of marked idiopathic hypovolemia with symptomatic labile hypertension and intolerance to head-up tilt, alleviated by volume expansion.

Adult↗
PubMed1986

Cardiovascular hypertrophy in spontaneously hypertensive rats.

In 1974 we reported that left ventricular mass correlated poorly with blood pressure levels during both the development and the reversal of hypertensive cardiac hypertrophy. This study, which was confirmed by many, has since been extended along two main lines: investigation of the factors modulating left ventricular hypertrophy and of associated changes in contractile protein, and comparison of the left ventricular structural response to hypertension with those of the large and small resistance vessels. In addition to blood pressure control, two factors were identified as important modulators of left ventricular hypertrophy: the level of cardioadrenergic activity and a recently isolated myocardial factor in SHR which stimulates in vitro cardiac protein synthesis. Of greater importance haemodynamically are the structural changes in the small resistance vessels; these were estimated from resistance to constant flow during maximal vasodilatation (Folkow). Captopril-hydrochlorothiazide led to a significantly greater reduction in that index than hydralazine, although both led to equal blood pressure control. Despite some general parallelism, the structural cardiovascular responses to hypertension were not homogeneous; important differences were found among the heart, aorta and resistance vessels. The development and regression of cardiovascular hypertrophy are not dependent on mechanical load alone but seem to be modulated at three levels - increased pressure load, level of cardioadrenergic activity and local growth factor.

Actomyosin↗