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Combined actions of isradipine and captopril on renal function in hypertension
L R Krusell1, I Sihm, L T Jespersen
1Department of Internal Medicine and Cardiology I, Aarhus Amtssygehus, Denmark.
Insights
Calcium-entry blockers like isradipine enhance sodium and uric acid excretion, potentially by blocking angiotensin II effects within the kidneys. This study investigated these effects in hypertensive patients already taking captopril.
Area of Science:
- Nephrology
- Cardiovascular Pharmacology
Background:
- Hypertension management often requires combination therapy.
- Calcium-entry blockers and angiotensin-converting enzyme inhibitors are common antihypertensives.
- The intrarenal mechanisms of calcium-entry blockers' natriuretic and uricosuric effects are not fully understood.
Purpose of the Study:
- To test if calcium-entry blockers' natriuretic and uricosuric effects are mediated by antagonism of angiotensin II-dependent intrarenal mechanisms.
- To investigate the antihypertensive, hemodynamic, and excretory effects of adding isradipine to captopril treatment in hypertensive patients.
Main Methods:
- Seven hypertensive patients with inadequately controlled blood pressure on captopril received escalating doses of isradipine.
- Renal function (GFR, RPF), electrolyte and uric acid clearances (Na, K, UA, Li), and hemodynamics were measured.
- Measurements were taken before and after low-dose isradipine bolus, during high-dose infusion, and after 4 months of combined therapy.
Main Results:
- A low dose of isradipine slightly increased sodium clearance (CNa) and heart rate.
- A high dose of isradipine significantly reduced blood pressure and renal vascular resistance, while increasing renal plasma flow (RPF) and natriuresis.
- Natriuresis resulted from proximal tubular action, indicated by increased lithium clearance (CLi).
Conclusions:
- Isradipine, a calcium-entry blocker, exhibits significant natriuretic and diuretic effects in hypertensive patients treated with captopril.
- These effects appear to be mediated, at least in part, through intrarenal mechanisms independent of systemic hemodynamics.
- The findings support the hypothesis that calcium-entry blockers may counteract angiotensin II-dependent intrarenal actions.
Abstract:
The object of this study was to test the hypothesis that the natriuretic and uricosuric effect of calcium-entry blockers could be mediated through antagonism of angiotensin II dependent intrarenal mechanisms. The antihypertensive efficacy, haemodynamic and excretional effects of superimposed calcium blockade with isradipine were investigated in seven hypertensives with unsatisfactorally controlled blood pressure with captopril 50 mg twice daily. Glomerular filtration rate (GFR) and renal plasma flow (RPF), clearances (C) of sodium (Na), potassium (K), uric acid (UA) and lithium (Li), were measured before and after a low-dose bolus of isradipine, i.v. Subsequently, measurements were repeated during constant i.v. infusion of a higher dose with definite systemic haemodynamic effects. After 4 months of combined treatment with isradipine and captopril renal investigations were carried out again. The low isradipine dose induced a slight but statistically significant increment in CNa (22% +/- 28) and heart rate (4% +/- 4), whereas no other variables changed significantly. Infusion of the high isradipine dose caused a pronounced fall in renal vascular resistance (27% +/- 14), systolic (8% +/- 2) and diastolic blood pressure (17% +/- 5). RPF increased significantly (15% +/- 18) whereas no changes were noted in GFR, filtration fraction and urinary albumin excretion rate. In spite of the pronounced fall in BP during the high dose infusion, significant increments in natriuresis (91% +/- 63) and diuresis (41% +/- 27) were induced. The natriuresis was caused by a proximal tubular action as indicated by increased CLi and CLi/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)