Vol. 286, Issue 2, 599-606, August 1998

Changes in Functional Expression of Alpha-1 Adrenoceptors in Hindlimb Vascular Bed of Spontaneously Hypertensive Rats and their Effects on Oxygen Consumption¹

Ji-Ming Ye and Eric Q. Colquhoun

Division of Biochemistry, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia 7001

Norepinephrine (NE) induces a sigmoidal dose-response curve for perfusion pressure and a bell-shaped curve for oxygen consumption (VO₂) in the constant-flow perfused hindlimb of Wistar rats. These effects are now described in spontaneously hypertensive rats (SHR) 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 µM propranolol, prazosin (2.5 nM) shifted the pressure and VO₂ curves much more than yohimbine (0.1 µM) to the right in both strains and its effects were greater in SHR, suggesting that these effects were mediated largely by alpha-1 receptors, particularly in SHR. In the presence of propranolol plus yohimbine, the pressure curve was markedly shifted to the right by both the selective alpha-1A-antagonist 5-methylurapidil (3.3 nM), and by the alpha-1D antagonist BMY 7378 (0.1 µM) or SK&F 105854 (2 µM) in SHR but not in WKY. With respect to the VO₂ curve, 5-methylurapidil attenuated the descending limb without affecting the ascending limb. Similar 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 inhibited the ascending limb of the VO₂ curve. These results indicate that both alpha-1A- and alpha-1D subtypes are functionally up-regulated in SHR muscle vascular bed where the ascending limb of VO₂ is predominantly mediated by the alpha-1D at a much lower concentration for NE than the descending limb which is predominantly mediated by the alpha-1A subtype.