Pre- and postjunctional inhibition of vascular sympathetic function by captopril in SHR. Implication of vascular angiotensin II in hypertension and antihypertensive actions of captopril.
The present study was designed to examine the effects of treatment of SHR with captopril, teprotide, and saralasin on vascular and cardiac responses to sympathetic nerve stimulation and angiotensin I and II (AI, AII) and norepinephrine (NE). A single dose of captopril (10 mg/kg i.v. as well as 10 and 100 mg/kg p.o.) caused significant and marked inhibition of pressor responses to sympathetic nerve stimulation in pithed SHR but cardiac responses were unaffected. Pressor responses to AI were abolished but those to AII and NE were not significantly altered. Neither teprotide nor saralasin caused consistent inhibition of sympathetic responses despite total blockade of AI and AII response respectively. Selective inhibition of pressor but not cardiac responses to sympathetic nerve stimulation was obtained after 2 weeks, 3 and 6 months of daily oral doses of captopril. In addition, postjunctional pressor responses to AI, AII, and NE were also significantly inhibited by chronic captopril treatment. Infusion of AII, bilateral nephrectomy, or pretreatment with indomethacin alone in pithed SHR receiving captopril had no effect on the inhibition of pressor responses to sympathetic stimulation. However, the combination of pretreatment of indomethacin and infusion of AII completely restored sympathetic function in SHR receiving captopril. These studies suggest that captopril has a selective inhibitory effect on vascular responses to sympathetic nerve stimulation but not on cardiac responses. Moreover, this effect may have a prejunctional component since, after acute treatment, there is no inhibitory effect on responses to AII or NE. Since, under appropriate conditions, the inhibition can be reversed by AII infusion but not nephrectomy, it is suggested that this inhibition occurs at the vascular level by inhibition of local AII formation by captopril, a site not accessible to teprotide or saralasin.
- Copyright © 1981 by American Heart Association