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Changes in functional expression of alpha-1 adrenoceptors in hindlimb vascular bed of spontaneously hypertensive rats and their effects on oxygen consumption
journal contributionposted on 2023-05-16, 11:10 authored by Ye, JM, Colquhoun, EQ
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 Î¼M propranolol, prazosin (2.5 nM) shifted the pressure and VO2 curves much more than yohimbine (0.1 Î¼M) 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 Î¼M) or SK and F 105854 (2 Î¼M) 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 and 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.
Publication titleJournal of Pharmacology and Experimental Therapeutics
Department/SchoolTasmanian School of Medicine
PublisherAmerican Society of Pharmacology and Experimental Therapeutics
Place of publicationBaltimore