CHANGES IN FUNCTIONAL EXPRESSION OF ALPHA-1-ADRENOCEPTORS IN HINDLIMBVASCULAR BED OF SPONTANEOUSLY HYPERTENSIVE RATS AND THEIR EFFECTS ON OXYGEN-CONSUMPTION

Norepinephrine (NE) induces a sigmoidal dose-response curve for perfus ion pressure and a bell-shaped curve for oxygen consumption (VO2) in t he constant-flow perfused hindlimb of Wistar rats. These effects are n ow described in spontaneously hypertensive rats (SHRJ and age-matched Wistar-Kyoto rats (WKY). In SHR, the pressure curve was shifted left- and upward whereas the VO2 curve was shifted left- but downward, when compared with WKY. In the presence of 10 mu M propranolol, prazosin (2 .5 nM) shifted the pressure and VO2 curves much more than yohimbine (0 .1 mu M) to the right in both strains and its effects were greater in SHR, suggesting that these effects were mediated largely by alpha-1 re ceptors, particularly in SHR. In the presence of propranolol plus yohi mbine, the pressure curve was markedly shifted to the right by both th e selective alpha-1A-antagonist 5-methylurapidil (3.3 nM), and by the alpha-1D antagonist BMY 7378 (0.1 mu M) or SK&F 105854 (2 mu M) in SHR but not in WKY. With respect to the VO2 curve, 5-methylurapidil atten uated the descending limb without affecting the ascending limb. Simila r effects were also obtained with another alpha-1A antagonist 1 nM KMD -3213 in both SHR and WKY. In contrast, BMY and SK&F markedly inhibite d the ascending limb of the VO2 curve. These results indicate that bot h alpha-1A-and alpha-1D subtypes are functionally up-regulated in SHR muscle vascular bed where the ascending limb of VO2 is predominantly m ediated by the alpha-1D at a much lower concentration for NE than the descending limb which is predominantly mediated by the alpha-1A subtyp e.