Cyclic adenosine monophosphate and vascular reactivity in spontaneously hypertensive rats

Role of stimulatory GTP‐binding protein (Gs) in reduced β‐adrenoceptor coupling in the femoral artery of spontaneously hypertensive rats

“…Although cyclic AMP levels were not actually measured in the present study, we think it is likely that the inhibition by either CTX or forskolin of the femoral arterial contraction is mediated through the elevation of cellular cyclic AMP. The inhibitory effect of forskolin was rapid in onset and dosedependent in a concentration range comparable with that seen in other tissues (Seamon & Daly, 1981;Daly, 1984 (Amer, 1973;Ramanathan & Shibata, 1974;Sands et al, 1976), increase (Dusseau & Hutchins, 1982;Chatelain et al, 1985) or remain unchanged (Triner et al, 1975), as compared with findings in WKY aortae. Studies by Triner et al (1975) demonstrated a decreased fi-adrenoceptormediated relaxation that coincided with a reduced production of cyclic AMP by the SHR in response to isoprenaline.…”

“…The major conclusion is that a reduced function of Gs is the main factor in the decreased responsiveness of the SHR femoral artery to fi-adrenoceptor stimulation. This is suggested by the following observations: (1) in the absence of f-adrenoceptor antagonists, contractile responses to NA were significantly greater in the SHR than in the WKY, (2) contractile responses to NA through the activation of a-adrenoceptors were the same for the two strains, (3) inhibitory effects of CTX on the a-adrenoceptormediated contractions were significantly weaker in the SHR than in the WKY, (4) contractile responses to a-adrenoceptor stimulation with NA determined after CTX-pretreatment were comparable to those determined in the absence of f-adrenoceptor antagonists in either the WKY or SHR, and (5) inhibitory effects of forskolin and db cyclic AMP on the a- (Amer, 1973;Amer et al, 1974;Triner et al, 1975;Cohen & Berkowitz, 1976;Asano et al, 1982;Silver et al, 1985). The decreased responsiveness to f-adrenoceptor stimulation was also observed in the dose-response curves of femoral arteries for the contractile effect of NA determined in the absence of fi-adrenoceptor antagonists (Figures 1 and 2).…”

“…Subsequently various studies have demonstrated a decreased responsiveness to fiadrenoceptor stimulation in vascular tissues from SHR (Cohen & Berkowitz, 1976;Asano et al, 1982;Silver et al, 1985). This decreased responsiveness of SHR vascular tissues may reflect a reduced activation of AC in the SHR (Amer, 1973;Triner et al, 1975;Klenerova et al, 1975). The studies by Amer (1973), Triner et al (1975 and Klenerova et al (1975) have demonstrated no change in basal activity of AC in the SHR aorta.…”

“…A consistent loss in responsiveness of vascular smooth muscles to fi-adrenoceptor stimulation has been demonstrated in a variety of hypertensive animals including spon- ' Author for correspondence. taneously hypertensive rats (SHR) (Amer, 1973;Amer et al, 1974;Triner et al, 1975;Cohen & Ber-kowitz, 1976; Asano et al, 1982;Silver et al, 1985).…”

Decreased arterial responsiveness to multiple cyclic AMP‐generating receptor agonists in spontaneously hypertensive rats

“…1973;Triner et al, 1975;Cohen & Berkowitz, 1976;Asano et al, 1982). In strips of the SHR femoral artery, the decreased (3-adrenoceptor responsiveness is reflected in an enhanced arterial contraction through the activation of a-adrenoceptors (Asano et al, 1982).…”