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Effect of amlodipine on renin secretion and renin gene expression in rats
K Schricker1, M Hamann, A Macher
1Physiologisches Institut, Universität Regensburg, Germany.
Abstract:
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.
Insights
Calcium channel blockade with amlodipine stimulates renin secretion and gene expression in rats. This effect is dose-dependent and additive to reduced renal perfusion pressure.
Area of Science:
- Pharmacology
- Renal Physiology
Background:
- Calcium channel blockers are widely used to treat hypertension.
- The effect of calcium channel blockade on renin secretion and gene expression requires further elucidation.
Purpose of the Study:
- To investigate the influence of amlodipine, a 1,4-dihydropyridine calcium channel blocker, on renin secretion and renin gene expression.
- To characterize these effects in both normal rats and rats with renovascular hypertension.
Main Methods:
- Administration of amlodipine at varying doses (5, 15, 45 mg/kg) to normotensive rats.
- Assessment of plasma renin activity and renal renin mRNA levels.
- Induction of renovascular hypertension using a 2-kidney-1-clip model.
- Evaluation of amlodipine's effects in hypertensive rats.
Main Results:
- In normotensive rats, amlodipine increased plasma renin activity and renin mRNA levels at higher doses (15 and 45 mg/kg), but not at 5 mg/kg.
- Amlodipine treatment also increased renin-immunoreactive areas in the kidney cortex.
- In 2-kidney-1-clip rats, amlodipine attenuated the rise in blood pressure and showed an additive effect on plasma renin activity.
- Renin mRNA levels in the clipped kidney tended to increase with amlodipine, while levels in the contralateral kidney remained suppressed.
Conclusions:
- Calcium channel blockade by amlodipine stimulates renin secretion and renin gene expression in vivo.
- These stimulatory effects are dose-dependent and can be additive to the effects of reduced renal perfusion pressure.