Premium
A study in the rat of the renal actions of nitrendipine and diltiazem on the adrenergic regulation of calcium and sodium reabsorption
Author(s) -
Johns Edward J.,
Manitius Jacek
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb11125.x
Subject(s) - nitrendipine , excretion , endocrinology , medicine , renal blood flow , diltiazem , chemistry , renal physiology , fractional excretion of sodium , blood pressure , calcium , renal function , hemodynamics
1 In pentobarbitone‐anaesthetized rats, intravenous administration of diltiazem at 5 μg kg −1 min −1 did not change blood pressure or renal blood flow but increased glomerular filtration rate by approximately 16%, urine flow by 85%, calcium excretion by 151% and absolute and fractional sodium excretions by 100% and 69%, respectively. A similar pattern of responses was obtained in renally denervated animals, except that calcium excretion did not change statistically. Diltiazem given at 20 μg kg −1 min −1 into renally innervated and denervated groups of animals depressed blood pressure between 15–17 mmHg but had no effect on renal haemodynamic or tubular function. 2 Nitrendipine administered at 0.5 μg kg −1 min −1 to renally innervated and denervated animals significantly depressed blood pressure in intact animals by 6 mmHg and in both groups did not change renal haemodynamics but caused similar increases in urine flow of between 79–98%, calcium excretion of between 87 and 125%, absolute sodium excretion of between 108 and 140% and fractional sodium excretion of between 83 and 170%. Infusion of nitrendipine at 1.0 μg kg −1 min −1 into intact or renally denervated animals decreased blood pressure by 18–20 mmHg and increased urine flow by 84–111%, calcium excretion by 85%, absolute sodium excretion by 81–137% and fractional sodium excretion by 52–102%. 3 Stimulation of the renal nerves at low frequencies (0.8 to 1.5 Hz) caused minimal changes in renal haemodynamics but decreased urine flow by 27%, calcium excretion by 35%, absolute and fractional sodium excretions 32% and 36%, respectively. In different groups of animals given either diltiazem at 20 μg kg −1 min −1 or nitrendipine at 0.5 μg kg −1 min −1 or l.0 μg kg −1 min −1 , a similar degree of renal nerve stimulation caused an identical pattern of excretory responses of similar magnitude to those obtained in the absence of drug. 4 The calciuretic, diuretic and natriuretic activities of diltiazem and nitrendipine were not dependent on renal nerves and probably represented a direct action on the tubular reabsorptive processes of these ions. The renal nerve‐induced increases in tubular calcium and sodium reabsorption indicate that these α‐adrenoceptor‐mediated responses are not dependent on the inward movement of calcium