Sympathetic function in spontaneously hypertensive rats after chronic administration of captopril.
The cardiovascular effects of electrical stimulation of the posterior hypothalamus, intravenous administration of norepinephrine (NE), and direct sympathetic nerve stimulation (SNS) were compared in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) given captopril (osmotic minipump, 1.25 micrograms/h icv) or vehicle for 4 wk beginning at age 7 wk. Mean arterial pressure (MAP) and renal and mesenteric flows (pulsed Doppler flow probes) were monitored in anesthetized rats. Following chronic administration of captopril the MAP was 141 +/- 4 mmHg in SHR receiving captopril and 183 +/- 6 mmHg in SHR receiving vehicle. Posterior hypothalamic stimulation, intravenous NE, and SNS resulted in lesser increases in MAP and renal and mesenteric vascular resistances in SHR treated with captopril. Response curves were shifted to the right, and the initial slopes and rate of change of slopes of the curves were less in captopril-treated SHR than vehicle-treated rats. The decrease in sensitivity to posterior hypothalamic stimulation was greater than the decrease in response to NE or SNS. The decrease in vascular reactivity in captopril-treated SHR was not due to increased sensitivity of the baroreflex for control of vascular resistance nor to a decrease in arterial pressure per se. WKY treated with captopril also showed lesser increases in MAP and renal and mesenteric vascular resistances in response to posterior hypothalamic stimulation, intravenous NE, and SNS. The depressor effects of intracerebroventricular captopril in SHR may be due, in part, to an attenuation in sympathetic vasoconstrictor tone. This attenuation involves both a decrease in vascular smooth muscle responsiveness to NE as well as a decrease in central stimulation of sympathetic outflow.
D000818:Animals; D001835:Body Weight; D002216:Captopril / Q000494:pharmacology*; D004558:Electric Stimulation; D006439:Hemodynamics; D006973:Hypertension / Q000503:physiopathology*; D007034:Hypothalamus, Posterior / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D012018:Reflex / Q000502:physiology; D012849:Sinoatrial Node / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014666:Vasomotor System / Q000503:physiopathology
D002216:Captopril; D009638:Norepinephrine