S. C. Textor

Redistribution of cardiac output to the kidneys during oral nadolol administration.

ALTHOUGH it has been demonstrated repeatedly that propranolol and other beta-blocking agents diminish heart rate and cardiac output, the role of these effects in determining regional perfusion unde...

Transient renal dysfunction during initial inhibition of converting enzyme in congestive heart failure.

Treatment with captopril in resistant normotensive congestive heart failure is associated with a pronounced reduction in blood pressure, particularly after the first dose. The effects of this reduction on renal function were assessed in 10 patients at the beginning of and during chronic treatment (at one week and three months). Renal plasma flow and glomerular filtration rates were measured by isotope clearance during water diuresis. The first dose of captopril (25 mg) led to a pronounced fall in renal plasma flow and glomerular filtration rates together with a decrease in mean arterial pressure; this fall correlated with baseline plasma renin activity. These changes were paralleled by decreases in water and sodium excretion. In contrast, by the end of the first week of treatment a similar fall in mean arterial pressure occurred together with a pronounced increase in renal plasma flow; the glomerular filtration rate was maintained and there was no decrease in water and sodium excretion. This new response pattern recurred after three months of treatment. The difference in response at different stages of treatment may reflect the balance between the different mechanisms influencing kidney dynamics in heart failure and their alteration by converting enzyme inhibition. The sustained increase in renal plasma flow during chronic treatment with captopril may account for the continued control of heart failure in these patients.

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.

Hemodynamic and antihypertensive effects of the new oral angiotensin-converting-enzyme inhibitor MK-421 (enalapril).

The antihypertensive, hemodynamic, and humoral effects of the new converting-enzyme inhibitor enalapril (MK-421) were assessed by sequential studies during 3 months of uninterrupted treatment (20 mg twice daily) in 10 hypertensive patients. Six achieved good blood pressure (mean arterial pressure) control with enalapril alone (from 126 +/- 7.0 mm Hg pretreatment to 105 +/- 1.6 mm Hg at 3 months, p less than 0.05). The other four required the addition of diuretics (hydrochlorothiazide 25 mg orally twice daily) at different stages of follow-up, with resultant blood pressure control (128 +/- 9.6 mm Hg pretreatment to 113 +/- 1.9 mm Hg at 2 months after the addition of diuretics). Neither the acute nor long-term blood pressure response could be predicted from the pretreatment levels of plasma renin activity. The blood pressure reduction during enalapril therapy was characterized by a decrease in total peripheral resistance (53 +/- 2.5 U X M2 pretreatment to 38 +/- 3.0 U X M2 at 3 months, p less than 0.05) with no significant change in cardiac output or heart rate. This lack of reflex tachycardia could not be ascribed to baroceptor dysfunction since the response to head-up tilt (the increase in diastolic blood pressure, in heart rate, and in plasma catecholamines) was normal and not significantly different from pretreatment response. Average blood volume did not change (91% +/- 4.3% of normal in the pretreatment period to 93% +/- 2.9% after 3 months of therapy, p = NS) despite the significant lowering of arterial pressure with enalapril alone (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and systemic hemodynamic effects of nitrendipine.

The antihypertensive effects of nitrendipine were evaluated in 12 subjects with hypertension, one of whom could not tolerate the drug for more than 3 days; hence hemodynamics were studied in the 11 subjects who were treated for 2 wk. In one patient taking 40 mg twice a day, blood pressure reduction was associated with a hemodynamic pattern of hyperkinetic circulation. Of the other 10 subjects, all of whom were taking 20 mg twice a day, two did not respond, but 8 had significant reduction in mean arterial pressure (136 ± 4.3 to 106 ± 3.2 mm Hg) resulting from a decrease in total peripheral resistance (52 ± 3.7 to 35 ± 2.6 U · m2). Changes in cardiac output, heart rate, and cardiopulmonary volume varied widely among subjects, such that average changes did not attain significance. Heart rate and cardiopulmonary volume, however, changed in the same direction, which suggests that the alterations in both were related to the degree of reflex sympathetic stimulation induced by nitrendipine. Plasma renin activity (PRA) increased during treatment (2.6 ± 1.0 to 9.3 ± 4.1 ng/ml/hr), whereas the increase in plasma aldosterone (PA) levels did not attain significance (13.7 ± 1.6 to 21.5 ± 4.5 ng/dl). As a result, PA/PRA decreased (16.1 ± 4.9 to 9.4 ± 2.6). These results suggest that calcium entry blockade might have interfered with steroidogenesis, thus blunting the effect of increased PRA. Finally, blood pressure response to nitrendipine in the whole group correlated inversely with pretreatment PRA (r = −0.88), suggesting greater activity of the drug in low‐renin hypertension.

Role of reactive hyperreninemia in blood pressure changes induced by sodium depletion in patients with refractory hypertension.

SUMMARY Sixteen patients with refractory hypertension were submitted to rigorous sodium depletion while cardloTascular bomeostasis was monitored with measurements of hormonal and bemodynamlc parameters and repeat saralasin tests. This regimen resulted in a negative sodium balance by an average of 300 mEq. The loss of sodium closely correlated to the decrease of body weight (r « 0.70, p < 0.005). Blood pressure (BP) decreased from 176/116 ± 8/3 to 155/109 ± 6/3 mm Hg. There was a significant correlation between percent increments in plasma renin activity (PRA) and the rise in plasma norepinephrine (r = 0.68, p < 0.05) and a dose negative correlation between percent increase in PRA and the ratio of fall in mean Mood pressure (MAP), per unit of weight loss (r = −0.73, p < 0.005). Thns, patients with the least percent increase In PRA demonstrated the greatest fall in BP per unit of weight loss, indicating that relative rather than absolute elevation of renin may be tne factor limiting antihypertenslve efficacy of sodium depletion. Sodium depletion induced increase in peripheral resistance and decrease in cardiac output, both mostly attributable to relative hyperreninemia. Indeed, the adverse hemodynamic changes were reversed by angiotensin inhibition, during which BP normalized. It is concluded that vigorous sodium depletion complemented by angiotensin blockade or suppression with sympatholytic agents improves management of otherwise refractory hypertension.

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)

Responses of the stenosed and contralateral kidneys to [Sar1, Thr8] AII in human renovascular hypertension.

To better define the intrarenal hemodynamic effects of angiotensin in human renovascular hypertension, 10 patients underwent renal hemodynamic and functional measurements before and during infusion of a competitive angiotensin analog, [Sar1, Thr8] AII. Eight had technically satisfactory split function studies. Despite a fall in mean arterial pressure (132 +/- 6 to 121 +/- 6 mm Hg, p less than 0.05) and humoral changes consistent with angiotensin-mediated hypertension, the intrarenal effects of this analog were commonly those of an angiotensin agonist, producing vasoconstriction and sodium retention. This was quantitatively greatest in the contralateral kidney, whose preinfusion sodium excretion (86 +/- 30 microEq/min vs 25 +/- 9 microEq/min, p less than 0.02) and glomerular filtration rate (76 +/- 7 ml/min vs 41 +/- 7 ml/min, p less than 0.01) were higher than the stenotic kidney. In some cases, an increase in renal blood flow and rise in sodium excretion were evident during angiotensin blockade, suggesting a tonic intrarenal action of angiotensin. Although renin vein renin values differed markedly between the stenotic and contralateral kidney (ratio = 2.05 +/- 0.30), relative changes in effective renal plasma flow were correlated (r = 0.84: p less than 0.01) during infusion of this analog. These results underscore the differences in sensitivities between vascular beds to the effects of angiotensin II and the major role of the contralateral kidney in renal function and sodium homeostasis in human renovascular hypertension.

Predictive Value of Angiotensin II Blockade With (sarcosine-1, Threonine-8) Angiotensin II In Renovascular Hypertension

Administration of an angiotensin II antagonist, (sarcosine-1, threonine-8) angiotensin II, was used to diagnose renovascular hypertension in 22 patients before renal revascularization or nephrectomy. Positive and negative responses to infusion occurred in 12 and 10 patients, respectively. Postoperatively, hypertension was cured in 13 patients, improved in 6 and unchanged in 3. The over-all accuracy of the infusion test in predicting the outcome of surgical therapy was 59 per cent, the false positive rate was 8.3 per cent and the false negative rate was 80 per cent. A similar high incidence of false negative results has been observed with differential renal vein plasma renin assays. The most accurate prediction of the blood pressure response to surgical therapy is obtained by considering multiple factors rather than a single test.

Home and office blood pressures. Clinical observations and hemodynamic mechanisms

Wide fluctuations in arterial pressure have long been recognized as a feature in many hypertensive patients and have consistently been a major difficulty in decisions for treatment and understanding of pathophysiology. It is only in the past decade that more precise estimates of the degree of diurnal variations could be obtained by ambulatory 24-hour recordings of blood pressure from intra-arterial catheterization (1) or noninvasive methods (2–3). In the absence of these methods, it is still possible to avoid the pitfalls associated with sole dependence on office blood pressure levels by asking the patients to measure their own pressures at home or at work. This was the method used for over forty years in our center; it had many advantages that could outweigh its limited number of daily observations. Blood pressure could be followed over long periods of time and not be limited to one day; the patients developed a greater sense of participating in their follow-up and came to recognize their pressure fluctuations as a physiolgoical variable analagous to changes in daily weight.