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Biomedical subjects

F H Leenen

Publications and source records attributed to F H Leenen.

13 recordsLinked to original sources
PubMed1979

Atenolol and chlorthalidone on blood pressure, heart rate, and plasma renin activity in hypertension.

The antihypertensive effect of atenolol, with and without chlorthalidone, on hypertension was assessed in an outpatient as well as in an inpatient study. In the outpatient study atenolol alone induced decreases in systolic and diastolic BP amounting to 20 and 15 mm Hg. Maximal response of BP and HR developed within a week at the lowest dose used (100 mg twice daily). Combined atenolol-chlorthalidone treatment decreased lying and standing systolic BP by 7 and 14 mm Hg more than atenolol alone, but diastolic BP was decreased little more. In the inpatient study the addition of atenolol to chlorthalidone therapy in a dose of 100 mg twice daily resulted in a maximal decrease in BP within 3 days. At this dose PRA was lowered only slightly. Larger doses did not lead to any significant further decrease in BP, whereas PRA fell progressively. Our results indicate that, in contrast to nonselective blockade, specific beta-1-adrenoceptor blockade by atenolol is capable of inducing a distinct antihypertensive effect, unrelated to suppression of PRA. The decrease in PRA after larger doses of atenolol was not accompanied by a further decrease in BP. Because diuretic-induced renin release plays a role in the maintenance of the BP, our findings suggest that at higher dosages a hypertensive effect of the beta blocker compensated for the hypotensive effect of the decrease in PRA.

Adult↗
PubMed1979

The influence of sar1 ala8 angiotensin II (saralasin) on plasma aldosterone in hypertensive patients.

The effect of a 4-hour infusion of the angiotensin II analogue sar1 ala8 angiotensin II (saralasin) on plasma aldosterone concentration (PAC) was assessed in relation to plasma renin activity (PRA) in 12 patients, both on normal sodium intake and after marked sodium depletion. On normal sodium intake the response of PAC to saralasin was variable; following sodium depletion saralasin induced a marked decrease in PAC in 11 of 12 patients. The extent of the change in PAC induced by saralasin correlated closely with log PRA. The data indicate that saralasin is also a competitive antagonist of the effect of the endogenous renin-angiotensin system (RAS) on the adrenal cortex, with agonistic activity appearing at low levels of PRA. The effect of sodium depletion on AC appears to be mediated to a major degree by the RAS.

Adrenal Cortex↗
PubMed1979

Possible significance of the pharmacological differentiation of beta-blockers for therapy of hypertension.

1 Cardioselective and non-selective beta-blockers affect to a different degree several aspects of the circulatory homeostasis. The evidence available in this regard has been evaluated and the possible clinical importance of these differences has been discussed. 2 Venous return in partly regulated by beta-receptors (possibly of the beta 2 type) in the venous resistance vessels. Differences in blockade of venous return by the two classes of beta-blockers may, therefore, influence the degree of increase in left ventricular size, left ventricular end diastolic BPs and stroke volume during beta-blockade. 3 At the first part of the dose-reponse curve, non-selective beta-blockers seem to block more effectively renin release than cardioselective beta-blockers. 4 The direction and the extent to which beta-blockers 'directly' affect total peripheral resistance (TPR), is determined by the resultant of the degree of decrease in TPR by blockade of renin release and the extent of the increase in TPR by blockade of the beta 2-receptors in the arteriolar wall. 5 The clinical relevance of these differences could be that--especially in the low doses range--non-selective beta-blockers may be more 'safe' in patients with compromised cardiac function and may be more appropriate for the therapy of high renin hypertension than cardioselective blockers, whereas the latter may be more appropriate for the majority of hypertensive patients who have low to normal renin hypertension.

Adrenergic beta-Antagonists↗
PubMed1979

Renin and aldosterone secretions during hypovolemia in rats: relation to NaCl intake.

Plasma renin activities (PRA) and aldosterone concentrations increased in parallel over a wide range of plasma volume deficits produced in unanesthetized rats by extravascular administration of polyethylene glycol (PEG) solution. When PEG-treated rats were given water to drink, their intakes were proportional to PRA; when given water and 0.5 M NaCl, PRA and the steroid concentrations diminished concurrently in association with sodium consumption. Aldosterone concentrations and NaCl intakes were markedly enhanced after PEG treatment in rats maintained on a sodium-deficient diet for 4 days. On the other hand, a clear relation between PRA and water intake, and between circulating aldosterone levels and sodium intake, was not suggested by other experiments in this series. For example, bilateral nephrectomy abolished the rise in PRA during hypovolemia yet rats drank water normally. Moreover, aldosterone concentrations were substantially elevated by PEG treatment in the nephrectomized rats yet sodium appetite was abolished. These and other findings suggest that neither angiotensin nor aldosterone plays a prominent role in stimulating water and saline intakes during hypovolemia.

Aldosterone↗
PubMed1979

Treatment of moderate to severe hypertensive patients with an orally active converting-enzyme inhibitor.

Seventeen hypertensive patients were treated with captopril, an orally active inhibitor of converting-enzyme. All patients showed a fall in blood pressure (BP), although in some patients only after the addition of diuretics. In 2 patients a skin rash developed. One patient developed proteinuria. A renal biopsy revealed membranous glomerulopathy. Correlations were found between pretreatment plasma renin activity (PRA) and the decrease in BP, and between pretreatment PRA and the decrease in plasma aldosterone concentration (PAC). Filtration fraction (FF) fell, indicating a decrease in renal vascular resistance. Captopril decreased the sensitivity to exogenous angiotensin I (AI), dependent on the captopril dose used. The sensitivity to exogenous bradykinin increased impressively even on the lowest dose of the drug. These observations suggest extrapulmonary conversion of AI to angiotensin II (AII).

Administration, Oral↗
PubMed1978

Angiotensin II blockade before and after marked sodium depletion in patients with hypertension.

1. Angiotensin II blockade before and after marked sodium depletion in patients with hypertension [unilateral renovascular (eight), bilateral renovascular (four) and essential (four)] was performed by intravenous administration of the angiotensin II antagonist Sar1-Ala8-angiotensin II (saralasin). 2. On normal sodium intake, saralasin decreased mean blood pressure by 8 mmHg in the unilateral renovascular group, by 6 mmHg in the bilateral renovascular group and increased it by 3 mmHg in the essential hypertensive group. After sodium depletion saralasin decreased mean blood pressure by 33 mmHg, 35 mmHg and 18 mmHg respectively. The saralasin-induced decrease in blood pressure significantly correlated with the log of the initial plasma renin activity. 3. Saralasin infusion decreased effective renal plasma flow (ERPF) in all three hypertension subgroups, both on normal sodium intake and after sodium depletion. Glomerular filtration rate decreased in direct relation to the hypotensive effect of saralasin but ERPF showed this relationship only after sodium depletion. On normal sodium intake saralasin increased filtration fraction by 17%, but decreased it by 7% after sodium depletion. 4. It is concluded that the hypotensive action of saralasin closely correlates with the value of circulating plasma renin activity, apparently independent of the aetiology of the hypertension. The decrease in ERPF during saralasin infusion in the patients on normal sodium intake seems mainly related to the agonistic activity of saralasin, but that after sodium depletion to the hypotensive effect of saralasin.

Adult↗
PubMed1978

Sodium intake and the effects of isoproterenol and exercise on plasma renin in man.

Changes in heart rate, blood pressure, and plasma renin activity (PRA) were assessed during infusion of increasing doses of isoproterenol and during increasing work loads of dynamic exercise in five normal young men. Studies were performed at three levels of dietary sodium restriction: normal, moderately, and more severely restricted. Isoproterenol induced the expected dose-related increases in heart rate, systolic blood pressure, and PRA and decreases in diastolic blood pressure. Changes in dietary sodium intake affected these changes only to a minor degree. Dynamic exercise also induced the expected work-load-related increases in heart rate, systolic blood pressure, and PRA and decreases in diastolic blood pressure. Also these changes were not significantly affected by changes in dietary sodium intake. Apparently dietary sodium restriction does not sensitize the renin-releasing mechanisms to sympathetic stimulation.

Adult↗
PubMed1977

Effects of hemodialysis and saline loading on body fluid compartments, plasma renin activity and blood pressure in patients on chronic hemodialysis.

The influence of one hemodialysis session and of subsequent loading by 1.5-2 liters N saline on blood pressure, PRA and body fluid compartments was assessed in seven patients with chronic renal failure on maintenance hemodialysis. Dialysis caused only slight decreases in plasma volume, ECV and in TEBS. Lying mean blood pressure by 5-10 mm Hg and PRA increased by 30%. Saline loading resulted in a significant increase in plasma volume by 0.4 liters and in blood pressure by 10-5 mm Hg, but in a decrease in PRA by 40%. The changes in mean blood pressure correlated positively with the changes in plasma volume, and negatively with the changes in PRA. It is concluded that the renin-angiotensin system in patients on chronic hemodialysis still functions as one of the adjustment mechanisms for the circulatory homeostasis, when challenged by volume loss or volume and sodium loading.

Adult↗
PubMed1975

Effect of salt depletion and propranolol on blood pressure and plasma renin activity in various forms of hypertension.

The effect of propranolol therapy on the mean arterial pressure (MAP) and plasma renin activity (PRA) was studied in three groups of hypertensive patients who were also treated with saliuretics. Group A: In 14 patients with essential hypertension on chlorthalidone treatment, an additional daily dose of 640 mg propranolol for two months led to a significant reduction of the MAP (from 124 to 105 mm Hg) and PRA (from 5.3 to 2.0 ng AI/ml/hr standing). There was no correlation between MAP reduction and either the original levels or change in PRA. Group B: In 14 patients with essential hypertension and 5 with renal artery stenosis studied on a fixed salt intake, the plasma and extracellular volumes, PRA, and blood pressures were recorded before and after three days of diuretic induced salt depletion and, with maintenance of the depleted state, after three days of propranolol. Salt depletion resulted in a decrease in MAP from 132 to 128 mm Hg (NS), and PRA increased from 3.4 to 22.3 ng AI/ml/hr (P less than 0.01). There was no correlation between change in MAP and PRA control values, PRA change, or any of the volume parameters. Addition of propranolol was followed by a rapid MAP decrease to 111 mm Hg (P less than 0.01), and the PRA dropped to a mean of 8.5 (P less than 0.01). No correlation was found between change in MAP and change in PRA. The patients with renal artery stenosis did not differ in their reactions from those with essential hypertension. Group C: In five patients with moderate renal failure and normal to expanded 82-Br distribution volume, propranolol lowered MAP by 10% and lowered the PRA in all five. Salt depletion by furosemide to 82-Br volumes below normal resulted in a 10% decrease of MAP and a marked rise in PRA. In this state propranolol was followed by a further MAP reduction of 18% and a decrease in PRA. There was no quantitative relationship between MAP and PRA change during either of the treatment regimes. It is concluded that in various forms of hypertension, the blood pressure can be effectively lowered by combining diuretics and propranolol regardless of the pretreatment PRA level.

Adult↗
PubMedDate not supplied

Effects of propranolol on development and maintanance of severe renal hypertension in rats.

1. The effect of chronic administration of propranolol on the development and maintenance of severe renal hypertension in rats subjected to unilateral renal artery constriction was studied in relation to possible changes in peripheral PRA and the blood and tissue levels of propranolol. Propranolol was administered s.c. twice daily in doses of 1, 10 and 25 mg/kg, starting 2 days before operation. 2. Contrary to expectations, not only did the initial rise in systolic blood pressure become accelerated, but the established level of hypertension attained in the propranolol treated rats was of the same severity as that attained in placebo treated rats. Moreover, the progressive rise in peripheral plasma renin activity following unilateral renal artery constriction was not affected by propranolol administration. 3. The same doses of propranolol were also administered daily for 8 days to rats with established severe hypertension. A slight further rise in blood pressure occurred initially, followed by a moderate decrease of 15-25 mmHg. Propranolol failed to exert this minor hypotensive effect in hypertensive rats treated concomitantly with furosemide. No suppressive effect on the markedly increased levels of plasma renin activity was observed in these severely hypertensive rats in the presence or absence of furosemide administration. 4. These results indicate that in severely renal hypertensive rats propranolol has only a minor hypotensive effect and no blocking action on renin release under the conditions of study.

Animals↗