PLASMA RENIN ACTIVITY IN STROKE-PRONE AND -RESISTANT SPONTANEOUSLY HYPERTENSIVE RATS: RELATIONSHIP TO SOME ANTIHYPERTENSIVE DRUGS

Abstract

Pepstatin (200μg/kg), clonidine (200μg/kg), phenoxybenzamine (POB) (1mg/kg or 3.5mg/kg) or propranolol (3mg/kg) was subcutaneously injected twice daily to male young Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) for consecutaive 14 days. It was found 1) that pepstatin failed to reduce the blood pressure in SHR and SHRSP, and PRA in these genetically hypertensive strains were similar to that of the saline-treated control animals. However, a slight decrease of blood pressure (6.2%, p<0.05) concomitant with an increase of PRA (81.5%), p<0.05) was observed in the pepstatin-treated WKY. 2) that there was a significantly lower blood pressure in clonidine-treated WKY (16.2%, p<0.001), SHR (22.6%, p<0.01) and SHRSP (37.7%, p<0.001) as compared to that of saline-treated räts; that PRA of WKY, but not that of SHR, or SHRSP, was decreased by treatment of clonidine (79.3%, p<0.01). 3) that lower dose of POB significantly (p<0.001) decreased blood pressure in WKY (11.5%), SHR (12.8%) and SHRSP (25.1%); that higher dosage of it caused significant (p<0.001) reduction of blood pressure and an increase of heart rate in each strain concomitant with remarkable increase (p<0.001) of PRA in WKY (328.5%), SHR (336.2%) and SHRSP (249.7%). 4) that blood pressure and heart rate of propranolol-treated WKY was similar to those of control rats, however PRA was lower than that of the control rats. Propranolol administration to SHR or SHRSP did not lower PRA, but caused bradycardia with a paradoxical rise in blood pressure in SHR at the age of 7 weeks (7.0%, p<0.001) or 8 weeks (7.3%, p<0.01) as well as 8-week-old SHRSP (5.8%, p<0.001).
These results indicate three important variables. First, renin-angiotensin system in young genetically hypertensive rats did not play an important role in the pathogenesis of genetic hypertension. Second, adrenergic receptor of WKY appeared to be more sensitive than that of SHR or SHRSP except the response of heart rates of SHR or SHRSP treated with propranolol. Third, pepstatin showed no hypotensive effect on SHR or SHRSP.