Biomedical subjects

I Kobrin

Publications and source records attributed to I Kobrin.

At least 55 records · Page 3Linked to original sources

PubMed1991

Limitations of the captopril test in the diagnosis of renovascular hypertension.

The captopril test has been suggested as a sensitive and specific noninvasive tool for the diagnosis of renovascular hypertension. We applied the test to 72 consecutive hypertensive patients in whom renal artery stenosis was suspected. The test was positive in seven cases (9.7%), of whom four were true positive and three false positive. The captopril test has value in screening for renovascular hypertension, but its limitations should be recognized. False positive results are not uncommon and false negative results have been reported under certain circumstances. Nevertheless, when properly applied to appropriate patients, the test can enhance the diagnosis of renal artery stenosis.

Adolescent↗

PubMed1990

Cardiac hypertrophy developing during DOCA-salt treatment is dissociated from systemic and regional hemodynamics.

Systemic and regional hemodynamics were studied in DOCA-treated Sabra hypertensive (SBH) and normotensive (SBN) rats. In SBH rats, mean arterial pressure (MAP) and total peripheral resistance index (TPRI) increased significantly. In SBN rats, MAP remained stable and TPRI decreased. Cardiac output and heart rate were unchanged. Opposed changes in TPRI were mediated mainly by changes in vascular resistance of the skin, skeletal muscles and splanchnic organs. Both strains developed significant biventricular hypertrophy. We conclude that SBH and SBN rats' susceptibility or resistance to DOCA-salt hypertension are associated with opposed changes in TPRI. The development of biventricular hypertrophy is apparently dissociated from systemic hemodynamic changes.

Animals↗

PubMed1989

Efficacy and safety of cilazapril in elderly patients with essential hypertension. A multicenter study.

The efficacy and safety of cilazapril monotherapy was evaluated in a multicenter, open-label, ascending-dose titration study in 83 elderly essential hypertensive patients. After a four-week, single-blind, placebo run-in period, patients received 1 mg of cilazapril once daily for the first four weeks. This dose was then increased to 2.5 mg once daily for the next four weeks for patients whose pre-dose sitting diastolic blood pressure was above 90 mm Hg. Similarly, at Week 8 the dose was increased in such patients from 1 to 2.5 mg or from 2.5 to 5 mg once daily. A 12-hour blood pressure profile was performed on the first day of active treatment and of each dose increase. Mean decrease of sitting diastolic blood pressure from baseline (102.7 +/- 0.4 mm Hg) at Week 12 was 13.3 +/- 1.1 mm Hg (p less than 0.001). Seventy-five percent of patients had a decrease of 10 mm Hg or more from baseline sitting diastolic blood pressure, and in 60 percent sitting diastolic blood pressure normalized. Unexpectedly large decreases of blood pressure after the first dose were seen only in three patients and none had clinical symptoms. Fourteen patients (16.9 percent) reported adverse events, but most of these were judged unlikely to be related to therapy. Four patients with predisposing underlying diseases experienced potentially serious adverse events (angina pectoris, myocardial infarction, arrhythmia, and blood pressure elevation) whose relationship to therapy was judged remote or only possible. There was no particular pattern of changes in laboratory values. The results indicate that cilazapril is an effective, safe, and well-tolerated antihypertensive drug for the elderly.

Aged↗

PubMed1988

Nitrendipine prevents the development of cardiac hypertrophy in DOCA-salt-treated hypertension-prone (SBH) and -resistant (SBN) rats through nonhemodynamic mechanisms.

Recent studies indicate that cardiac and renal hypertrophy develop during desoxycorticosterone acetate (DOCA)-salt (DOC) treatment in hypertension-prone (SBH) and -resistant (SBN) rats, irrespective of systemic hemodynamic changes. The effect of nitrendipine on the development of left and right ventricular hypertrophy (LVH and RVH, respectively) was evaluated in 16-week-old rats. Members of each strain were divided into six groups (n = 10): 1--control; 2--nitrendipine treated for 3 weeks; 3, 4, and 5--DOC for 10 days, 3 weeks, and 6 weeks, respectively; 6--DOC for 6 weeks and nitrendipine for the last 3 weeks. Cannulae were inserted into the left ventricle and abdominal aorta. The radioactive reference sample microsphere technique was used to measure cardiac index. Mean arterial pressure (MAP) and total peripheral resistance index (TPRI) were unchanged in all six groups of SBN rats, whereas MAP and TPRI increased progressively in the DOC-treated SBH groups. Concomitant administration of nitrendipine in Group 6 was associated with a reduction of MAP and TPRI to control levels. Cardiac index and heart rate did not change in any group. Despite the different hemodynamic changes, both SBH and SBN rats developed LVH and RVH. The concomitant administration of nitrendipine prevented the progression of LVH and allowed regression of RVH in both strains. It is concluded that nitrendipine can affect the pathogenesis of LVH through nonhemodynamic mechanisms.

Animals↗

PubMed1987

Time course of regression of left ventricular hypertrophy in hypertensive patients treated with atenolol.

Regression of left ventricular hypertrophy occurs with a number of antihypertensive drugs, but the time course of this regression has not been defined clearly. We obtained echocardiograms at baseline and serially (on seven occasions) during a 1 year treatment period with the beta-adrenergic receptor inhibitor atenolol in 12 patients with previously untreated essential hypertension. To ensure control of blood pressure in all patients throughout the study, it was necessary to add a thiazide diuretic to the therapy of five patients. Baseline blood pressure was 155/100 mm Hg and fell to 136/84 mm Hg; there was a 20% reduction in heart rate. Posterior and septal wall thicknesses were reduced from 1.16 +/- 0.03 to 1.06 +/- 0.02 cm (p less than .05) and from 1.28 +/- 0.07 to 1.18 +/- 0.06 cm (p less than .05), respectively; this reduction became significant initially at 4 weeks. Left ventricular mass decreased from 144 +/- 9 to 127 +/- 7 g/m2 (p less than .05) and this fall first became statistically significant at 6 months. Significant reduction in electrocardiographic voltages was also seen at 6 months. Therefore, regression of left ventricular hypertrophy with atenolol-induced blood pressure control occurred as early as 4 weeks after starting therapy and was maintained thereafter without apparent compromise of left ventricular systolic function.

Adult↗

PubMed1986

The effect of prolonged administration of CGS 10078B on systemic and regional haemodynamics in normotensive and spontaneously hypertensive rats.

The effects of 3 weeks treatment with CGS 10078B (30 mg/kg orally) on systemic and regional haemodynamics and cardiac mass were studied in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The significant decrease in mean arterial pressure (MAP) (174 +/- 3 versus 156 +/- 4 mmHg, P less than 0.002) in SHR was associated with a significantly slower heart rate. No significant alteration in systemic haemodynamics was observed in WKY rats. The reduced MAP in SHR was related to the preserved blood flow to the vital organs, and therefore reduced renal and cerebrovascular resistances. Left ventricular mass index was reduced in both rat strains of treated animals. Therefore, the reduced MAP and heart rate in the SHR without haemodynamic changes in the WKY indicates that CGS 10078B was an effective antihypertensive agent that decreased cardiac mass in rats through mechanisms that may be dissociated from their haemodynamic effects.

Adrenergic alpha-Antagonists↗

PubMed1986

Immediate and short-term hemodynamic effects of diltiazem in patients with hypertension.

The immediate effects of intravenous diltiazem effects and short-term (4 weeks) of the oral drug on systemic and regional hemodynamics, cardiac structure, and humoral responses were evaluated by previously reported methods in nine patients with mild-to-moderate essential hypertension and in one patient with primary aldosteronism. Diltiazem was first administered in three intravenous doses of 0.06, 0.06, and 0.12 mg/kg, respectively; patients were then treated for 4 weeks with daily doses ranging from 240 to 360 mg (average 300 mg). Intravenous diltiazem immediately reduced mean arterial pressure (from 115 +/- 3 to 96 +/- 3 mm Hg; p less than .01) through a fall in total peripheral resistance index (from 37 +/- 3 to 23 +/- 2 U/m2; p less than .01) that was associated with an increase in heart rate (from 66 +/- 2 to 77 +/- 3 beats/min; p less than .01) and cardiac index (from 3.3 +/- 0.3 to 4.3 +/- 0.4 liters/min/m2; p less than .01). These changes were not associated with changes in plasma levels of catecholamines or aldosterone or in plasma renin activity. After 4 weeks the significant decrease in mean arterial pressure persisted (104 +/- 3 mm Hg; p less than .01) and there were still no changes in the humoral substances or plasma volume. Renal blood flow index increased (from 368 +/- 52 to 462 +/- 57 ml/min/m2; p less than .01) and renal vascular resistance index decreased (from 0.37 +/- 0.06 to 0.26 +/- 0.04 U/m2; p less than .01), while splanchnic hemodynamics did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Renal involvement follows cardiac enlargement in essential hypertension.

To assess the relationship between early clinically detectable involvement of hypertensive vascular disease in heart and kidneys, we obtained systemic and renal hemodynamic and M-mode echocardiographic measurements in 65 patients with essential hypertension. The results indicate that patients with and without left ventricular hypertrophy had similar renal hemodynamic findings. In contrast, patients with altered renal hemodynamic measurements (ie, reduced renal distribution of cardiac output and, therefore, absolute renal blood flow with increased renal vascular resistance) and increased serum uric acid levels also had increased left ventricular posterior and septal wall thicknesses and mass index. Moreover, these data also demonstrated that in patients with altered renal hemodynamics, the lower the renal distribution of cardiac output and the higher the serum uric acid levels, the greater were the indexes of cardiac enlargement. These results demonstrated that the pathophysiological and hemodynamic effects of essential hypertension in the heart precede those in the kidneys.

Adult↗

PubMed1986

Baroreflex control of heart rate after immediate and prolonged pressure reduction with urapidil in conscious normotensive and spontaneously hypertensive rats.

Baroreflex control of heart rate was studied in conscious normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats before and after acute and prolonged arterial pressure reduction with urapidil, a central and peripheral inhibitor of adrenergic function. While immediate treatment (1 mg/kg i.v.) caused significant reduction in mean arterial pressure (MAP) in both strains, prolonged treatment (20 mg/kg daily by gastric tube for 3 weeks) reduced MAP in the SH rats only. Following an i.v. bolus injection of norepinephrine (10 micrograms/kg) before each mode of treatment, and after immediate and prolonged treatment with urapidil, similar increases in MAP were observed in both strains, but only prolonged MAP reduction caused a significantly increased sensitivity of the reflex control of heart rate in SH rats (P less than 0.01). It is concluded that prolonged, but not immediate, reduction in MAP with urapidil was associated with a significant increase in the baroreflex sensitivity in the hypertensive strain. This may be related to the central effects of the drug.

Animals↗

PubMed1985

Cardiovascular effects and regional blood flow distribution associated with angiotensin converting enzyme inhibition (captopril) in essential hypertension.

Systemic and regional hemodynamics and cardiac structural changes were studied in 12 patients with mild to moderately severe essential hypertension before and then 90 minutes and 12 weeks after administration of captopril. Mean arterial pressure was reduced from 111 mm Hg to 96 mm Hg (p less than 0.001), and this was mediated through a fall in total peripheral resistance from 26 +/- 2 units to 23 +/- 2 units (p less than 0.01). The decreased total peripheral resistance was distributed to all circulations studied: kidney, skeletal muscle, skin and the splanchnic organs. Furthermore, left ventricular (LV) mass index diminished without altering myocardial contractility at rest. Thus, captopril lowered arterial pressure through systemic arteriolar dilatation in patients with mild to moderately severe essential hypertension and also reduced LV mass even in patients without evidence of LV hypertrophy.

Adult↗

PubMed1985

Immediate hemodynamic effects of urapidil in patients with essential hypertension.

Systemic, renal and splanchnic hemodynamics and certain reflex and endocrine responses were determined in 10 patients with essential hypertension before and after intravenous administration of urapidil, a new antihypertensive agent that acts through both central and peripheral alpha-adrenergic inhibitory mechanisms. The reduction in mean arterial pressure by 12% (103 +/- 3 vs 91 +/- 6 mm Hg, p less than 0.05) was mediated through a decreased total peripheral resistance index (from 34 +/- 2 to 25 +/- 3 U/m2, p less than 0.01), which was associated with a significant reflexive increase in cardiac index, heart rate and serum norepinephrine level. This hypotensive effect was also associated with blunted Valsalva overshoot and orthostatic hypotension, suggesting peripheral arteriolar and venular dilation. Renal and splanchnic blood flows increased (p less than 0.05), resistances in these vascular beds decreased (p less than 0.01) and there were no changes in creatinine clearance or glomerular filtration fraction. Thus, intravenous urapidil reduced arterial pressure by decreasing total peripheral, renal and splanchnic resistances associated with maintained organ flows and increased heart rate and cardiac index.

Antihypertensive Agents↗

PubMed1985

Hemodynamic effects of a new alpha- and beta-adrenergic receptor inhibitor with calcium entry blocking effects (CGS 10078B) in WKY and SHR rats.

The immediate acute hemodynamic effects of CGS 10078B, a new agent with combined alpha- and beta-adrenergic antagonist with slow channel calcium entry blocking effects, were studied in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), total peripheral resistance index (TPRI), and regional hemodynamic measurements were determined before and two hours after its administration (10 mg/kg, gavage) using the combined radioactive reference sample and microsphere techniques (85SR and 141Ce). The agent significantly reduced MAP (168 +/- 5 to 158 +/- 5 mm Hg; p less than 0.02) after 20 minutes without changing HR in SHR. After two hours MAP, HR, and Cl were significantly reduced without change in TPRI. Only Cl decreased (p less than 0.05) in WKY, presumably from its beta receptor antagonist effects. Blood flow to the major organs (eg, heart, brain, and kidneys) was maintained in both groups of rats. These hemodynamic effects reflect the combined actions of this new agent and suggest its potential value for the treatment of hypertension.

Adrenergic alpha-Antagonists↗

PubMed1985

Renal response to acute volume overload in conscious rats with atrial appendectomy.

The presence of volume receptors and a potent natriuretic factor (ANF) in mammalian cardiac atria strongly suggests a central role of the atria in extracellular fluid volume regulation. ANF is stored within granules in atrial appendages, and their removal could alter the response to volume overload. We tested this hypothesis in conscious Wistar rats two weeks after sham operative or atrial appendectomy. The results indicate that removal of the atrial appendages significantly reduced their urinary excretion of water, sodium and potassium during the first hour following acute volume overload. It is concluded that atrial appendectomy alters the ability of rats to handle acute volume overload possibly through a reduction in the ANF available for release.

Animals↗

PubMed1985

Acute pressure increase and intrarenal hemodynamics in conscious WKY and SHR rats.

Spontaneously hypertensive rats (SHR) develop proteinuria and glomerular lesions during the first year of their life. To determine whether an intrarenal hemodynamic abnormality might participate in the pathogenesis of these lesions, normotensive Wistar-Kyoto (WKY) and SHR rats were subjected to acute pressure increase with phenylephrine infusion (2.5 and 5 micrograms X kg-1 X min-1), and renal blood flow (RBF), afferent and efferent arteriolar resistances, glomerular filtration rate (GFR), and glomerular capillary hydrostatic pressure were measured or calculated. The results indicate that the two strains responded differently to the pressure rise. Thus, although the increment in renal perfusion pressure and afferent arteriolar resistance increased similarly in the two strains, efferent resistance increased only in the SHR (7.2 +/- 1.6 vs. 9.0 +/- 2.1 units, P less than 0.02) but decreased in the WKY (5.3 +/- 0.8 vs. 4.0 +/- 0.5 units, P less than 0.05). This was associated with a decreased RBF of SHR (8.31 +/- 0.71 vs. 7.22 +/- 0.57 ml X min-1 X g kidney-1, P less than 0.05) but stable RBF in WKY (7.36 +/- 0.55 vs. 7.79 +/- 0.51 ml X min-1 X g kidney-1); GFR remained unchanged in both strains. Calculated glomerular hydrostatic pressure, however, increased in the SHR (43.6 +/- 3.0 vs. 48.5 +/- 2.2 mmHg, P less than 0.05) but decreased in the WKY (33.2 +/- 2.5 vs. 28.8 +/- 1.7 mmHg, P less than 0.01). The observed higher base-line glomerular pressure in the SHR and a greater rise with phenylephrine infusion may participate in the pathogenesis of the SHR glomerular lesions and proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Disparate cardiac effects of afterload reduction in hypertension.

Cardiac performance, as judged by preload, afterload, and myocardial contractility, was evaluated by non-invasive M-mode echocardiography before and after acute oral administration of calcium entry blockers (nitrendipine and verapamil), angiotensin converting enzyme (ACE) inhibitors (captopril and lisinopril), and a dopamine receptor agonist (fenoldopam) in patients with mild to moderate essential hypertension. Left ventricular end diastolic volume was taken as an index of preload, end systolic stress as an index of afterload, and the ratio of systolic pressure to end systolic volume (SBP:ESV), ejection fraction (EF), and mean velocity of circumferential fibre shortening (Vcf) as indices of contractility. Reductions of afterload and mean arterial pressure were achieved with all antihypertensive agents involved (mean percentage change +/- s.e.m.: 15 +/- 2% and 10 +/- 1%, respectively, P < 0.05) but the afterload reduction with lisinopril was greatest (21 +/- 9%; P < 0.01). The dopamine receptor agonist fenoldopam decreased by preload 24% (P < 0.05) and increased all of the three parameters of myocardial contractility (SBP:SV 66%; EF 17%, Vcf 19%; P < 0.01). In contrast, no effect on these parameters was observed with either calcium entry blocker or either ACE inhibitor.

Adult↗

PubMed1984

Systemic and regional hemodynamic effects of acute and prolonged treatment with urapidil or prazosin in normotensive and spontaneously hypertensive rats.

The regional and systemic hemodynamics of urapidil and prazosin were investigated after intravenous (1 mg/kg or 0.01 mg/kg, respectively) and prolonged (three weeks) oral treatment (20 mg/kg a day or 2 mg/kg a day, respectively) in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Following intravenous administration, both urapidil and prazosin decreased mean arterial pressure, mediated through a decrease in total peripheral resistance and accompanied by a transient increase in heart rate in both strains. The changes in regional circulations were more widespread after urapidil, but of longer duration after prazosin. Prolonged administration of urapidil or prazosin resulted in a significant decrease in mean arterial pressure and total peripheral resistance only in SHR. With urapidil treatment, the decrease in vascular resistance was distributed throughout all circulations, with no change in heart rate or cardiac index. Heart rate increased in WKY rats and cardiac index increased in SHR following prazosin treatment. Cardiac mass remained unchanged following treatment with either drug.

Animals↗

PubMed1984

Immediate regional blood flow distribution following angiotensin converting enzyme inhibition in patients with essential hypertension.

The increased total peripheral resistance that characterizes essential hypertension is generally reversed by antihypertensive drugs, but the reduction may not be uniform in all regions of the body. In this study, regional blood flow was investigated immediately after the oral administration of 25 mg of captopril in 11 patients with mild to moderate essential hypertension. Within 90 minutes, the total vascular resistance decreased significantly, and the decrease was significant in the kidney. It decreased but not significantly in the splanchnic organs, the skeletal musculature, and the skin. In no region was the blood flow reduced. As captopril has no direct effect on smooth muscle, these effects are likely to have been due to angiotensin converting enzyme inhibition.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1984

Enalapril improves systemic and renal hemodynamics and allows regression of left ventricular mass in essential hypertension.

Enalapril, a new angiotensin-converting enzyme inhibitor, is an effective antihypertensive agent for both renovascular and essential hypertension. It is structurally different from captopril in that it does not possess a sulfhydryl group. The systemic and renal hemodynamic, biochemical and cardiac adaptive changes induced by enalapril were studied in 8 patients with essential hypertension before and after 12 weeks of therapy. Mean arterial pressure decreased from 110 to 90 mm Hg (p less than 0.01), and this was mediated through a decrease in total peripheral resistance from 42 +/- 3 to 32 +/- 3 U (p less than 0.01). Cardiac index and heart rate did not change. Renal plasma flow was increased in 6 of 8 patients and renal vascular resistance decreased from 123 +/- 6 to 91 +/- 7 U (p less than 0.001). Left ventricular mass index decreased from a mean of 166 +/- 29 to 117 +/- 8 g/m2 (p less than 0.05) without impaired myocardial contractility. Thus, enalapril lowers arterial pressure by reducing total peripheral resistance without reflexive cardiac effects. It also has favorable hemodynamic effects on the kidney. This is the first report of regression of LV mass with this agent in man.

Adult↗