Renal effects of 1,4-dihydropyridines in animal models of hypertension and renal failure.

Renal effects of 1,4-dihydropyridine (DHP)-type calcium antagonists (nitrendipine and nisoldipine) were analyzed in diverse conditions, such as long-term antihypertensive treatment, acute saline-loading, and acute renal failure in rats. In spontaneously hypertensive rats (SHR), 60-week treatment with nitrendipine resulted in normotensive blood pressure values without increasing body weight, an indicator of salt-water retention, or increasing plasma renin activity and plasma aldosterone concentration compared with the untreated rats. After acute saline-loading of normotensive or hypertensive rats, administration of calcium antagonists nitrendipine and nisoldipine increased urinary volume and sodium excretion. This was in contrast to the effects observed with the vasodilator minoxidil, with which salt-water retention was shown. In acute renal failure induced by 60-min renal ischemia in uninephrectomized rats, administration of nisoldipine decreased mortality rate and improved kidney function. The increase in renal tissue calcium content and the decrease in ATP content associated with the renal failure was abolished by nisoldipine treatment. In conclusion, renal protective effects are present with DHP-type calcium antagonists; however, mechanisms in situations such as hypertension or acute renal failure might be different and deserve further analysis.