Effects of dihydropyridine Ca blockers on the renal function in nephrotic spontaneously hypertensive rat (SHR)

An animal model having both hypertension and reduced renal function was produced by intraperitoneal injection of puromycin aminonucleoside (PAN) in spontaneously hypertensive rat (SHR). Using this model, two different dihydropyridine Ca blockers, CS-905 and nicardipine, were compared with regard to the relationship between hypotensive effects and changes in renal function in a conscious state. A single oral administration of CS-905 or nicardipine at doses of 3 or 10 mg/kg produced a dose-dependent decrease in blood pressure and an increase in heart rate. Glomerular filtration rate (GFR) was decreased only at 10 mg/kg. However, there was a substantial difference between the two drugs with respect to the relationship between blood pressure and GFR. The decrease of GFR by nicardipine was observed when blood pressure was at the lowest level, while GFR decreased by CS-905 returned to the initial level when blood pressure reached a nadir. Percent decrease of GFR by CS-905 was significantly less than that by nicardipine although both agents produced almost the same degree of peak hypotension. These results suggest the decrease in GFR by Ca blockers depends not only on the degree of hypotension but other factors as well, such as the rate of blood pressure lowering. Despite the hypotension, both agents produced a marked natriuresis. Since the natriuresis was not accompanied by an increase in GFR, it was assumed that the natriuretic effect of Ca blockers stemmed from their tubular effects rather than glomerular ones.