Hypotensive action of captopril in spontaneously hypertensive and normotensive rats. Interference with neurogenic vasoconstriction.
The effects of captopril and angiotensin II on adrenergic neurotransmission have been studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In a pithed rat preparation, vasoconstrictor responses evoked by spinal stimulation were greater in SHR than WKY (p less than 0.01). Captopril reduced responses to electrical stimulation and this reduction was greater in the SHR (p less than 0.001). Bilateral nephrectomy reduced the vasoconstrictor responses to nerve stimulation in both strains of rat and abolished the effects of captopril. In an isolated perfused mesenteric artery WKY (p less than 0.05). Angiotensin II potentiated responses from both strains of rat, however the amplitude of the potentiation was greater in preparations from the SHR than those from WKY (p less than 0.002). Captopril (30 mg/kg by mouth) reduced blood pressure in conscious SHR over a 5-day dosing period. In WKY rats, no hypertensive action of captopril was observed. However, in another normotensive strain, the Alderley Park Wistar rat (APW), captopril lowered blood pressure. Plasma renin activity was not significantly different among these three strains of rat. The APW have previously been shown to be very sensitive to the adrenergic potentiating actions of angiotensin II. Captopril thus lowers blood pressure in SHR and APW, and both these strains are sensitive to the adrenergic potentiating actions of angiotensin II. It does not lower blood pressure in WKY, which is relatively insensitive to these actions of the octapeptide. Therefore, the hypotensive action of captopril in the rat may be due to its interference with the adrenergic potentiating effect of angiotensin II.
D000320:Adrenergic Fibers / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D007022:Hypotension / Q000139:chemically induced*; D008638:Mesenteric Arteries / Q000294:innervation; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D009435:Synaptic Transmission; D014661:Vasoconstriction / Q000187:drug effects*
D000804:Angiotensin II; D011392:Proline; D002216:Captopril; D012083:Renin