A study of the renal actions of amlodipine in the normotensive and spontaneously hypertensive rat.
1. Normotensive Sprague-Dawley and spontaneously hypertensive rats anaesthetized with sodium pentobarbitone were used to determine the systemic and renal actions of amlodipine, a new calcium channel blocking drug. 2. Amlodipine, 200 micrograms kg-1 plus 50 micrograms kg-1 h-1, decreased blood pressure by 12 +/- 3 mmHg in normotensive rats, although the fall was not statistically significant in the hypertensive rats; did not change renal haemodynamics and caused significant increases in urine flow, absolute and fractional sodium excretions of 70%, 91% and 113%, respectively, in normotensive rats and 65%, 91% and 96%, respectively in hypertensive rats. Fractional lithium excretion was unchanged in the normotensive rats but increased by 28% in the hypertensive animals while absolute fluid reabsorption in the proximal tubule did not change in either group. Absolute water and sodium reabsorption in the segments beyond the proximal tubule were unchanged in the normotensive rats but increased in the hypertensive animals by 24% and 22%, respectively, while fractional sodium excretion in this portion of the nephron increased by 88% and 51% in the normotensive and hypertensive rats, respectively. 3. Amlodipine, 400 micrograms kg-1 plus 100 micrograms kg-1 h-1, decreased blood pressure by 12 +/- 4 mmHg in the normotensive and by 27 +/- 5 mmHg in the hypertensive rats. Renal blood flow was not changed in either group of rats and glomerular filtration rate increased by 25% in the spontaneously hypertensive animals. There were significant increases in urine flow, absolute and fractional sodium excretions of 105%, 145% and 142%, respectively, in the normotensive rats and 224%, 421% and 259%, respectively, in the hypertensive rats. Renal blood flow was not changed in either group of rats and glomerular filtration rate increased by 25% in the spontaneously hypertensive animals. There were significant increases in urine flow, absolute and fractional sodium excretions of 105%, 145% and 142%, respectively, in the normotensive rats and 224%, 421% and 259%, respectively, in the hypertensive rats. Fractional lithium excretion was elevated by 29% and 38%, in the normotensive and hypertensive rats, respectively, but absolute fluid reabsorption at the proximal tubule remained unchanged. At the same time there were significant increases in absolute water and sodium reabsorption beyond the proximal tubule of 26% and 18%, respectively, in the normotensive animals and of 63% and 60%, respectively, in the hypertensive animals. Fractional excretion of water and sodium in the nephron regions after the proximal tubule were increased by 55% and 88%, respectively, in the normotensive rats and by 84% and 121%, respectively, in the hypertensive rats. 4. These doses of amlodipine caused modest reductions in blood pressure, minimal changes in renal haemodynamics and a natriuresis and diuresis. Proximal sodium and water reabsorption was not affected by the drug and it is suggested that the changes in tubular fluid handling were compatible with depression of reabsorption further along the tubule.
Johns
E J
EJ
Department of Physiology, Medical School, Birmingham.
D017311:Amlodipine; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D007684:Kidney Tubules / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000502:physiology; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine