Effect of amlodipine on renin secretion and renin gene expression in rats.
1. This study was done to characterize the influence of calcium channel blockade on renin secretion and renin gene expression in normal rats and rats with renovascular hypertension. To this end we studied the effects of the 1,4-dihydropyridine derivative, amlodipine, on plasma renin activity and renal renin m-RNA levels in normal rats and rats with unilateral renal hypoperfusion induced by applying 0.2 mm left renal artery clips over four days. 2. In normotensive rats, amlodipine significantly decreased basal blood pressure by about 20 mmHg when applied in a concentration of 5, 15 and 45 mg kg-1. Plasma renin activity and also renin mRNA levels were not changed after application of 5 mg kg-1 of amlodipine. However, at a concentration of 15 or 45 mg kg-1, amlodipine, significantly increased not only plasma renin activity by about 250% and 300%, but also renin mRNA levels by about 100% and 500%. The action of amlodipine on all these parameters was maximal after 24 h. Treatment with amlodipine in a concentration of 15 mg kg-1 also increased renin immunoreactive areas in the kidney cortex by retrograde recruitment of renin expressing cells in the afferent arterioles. 3. In 2kidney-1 clip rats, systolic blood pressure rose continuously whilst plasma renin activity and renin m-RNA in the clipped kidney increased transiently and renin m-RNA in the contralateral kidney was constantly suppressed. Amlodipine at a concentration of 15 mg kg-1 markedly attenuated the increase of blood pressure in 2kidney-1 clip rats, produced an almost additive effect on plasma renin activity and showed a tendency to increase renin m-RNA levels in the clipped kidneys. Renin m-RNA levels in the contralateral kidney were also significantly suppressed in the animals receiving additional treatment with amlodipine. 4. These findings suggest that inhibition of calcium channels by amlodipine stimulates renin secretion and renin gene expression in vivo. These stimulatory effects are almost additive to the changes of renin secretion occurring after an unilateral fall of renal perfusion pressure.
Physiologisches Institut, Universität Regensburg, Germany.
K
K
Schricker
M
M
Hamann
A
A
Macher
B K
BK
Krämer
B
B
Kaissling
A
A
Kurtz
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006978:Hypertension, Renovascular / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics / Q000378:metabolism*
D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D017311:Amlodipine; D012083:Renin