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Decreased arterial responsiveness to multiple cyclic AMP‐generating receptor agonists in spontaneously hypertensive rats
Author(s) -
Masuzawa Kaoru,
Matsuda Tomohiro,
Asano Masahisa
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11804.x
Subject(s) - medicine , endocrinology , cyclic gmp , receptor , pharmacology , chemistry , nitric oxide
1 Arterial relaxant responses via β‐adrenoceptors are decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar‐Kyoto rats (WKY). Recent studies from this laboratory proposed that a reduced function of stimulatory guanosine 5′‐triphosphate (GTP)‐binding protein (Gs) is responsible for the decreased β‐adrenoceptor responsiveness in the SHR femoral artery. Since the Gs is common to all tissues, as opposed to receptors, which are tissue specific, the reduced function of Gs should lead to resistance to multiple receptors that act by activating adenylate cyclase (AC). To test this hypothesis, relaxant responses via β‐adrenoceptors, A 2 ‐adenosine, H 2 ‐histamine and D 1 ‐dopamine receptors were compared between arterial strips from 13 week‐old WKY and age‐matched SHR. 2 The relaxant responses to noradrenaline (NA) via β‐adrenoceptors in femoral, mesenteric, renal and carotid arteries were significantly decreased in the SHR, when compared with the respective arteries from WKY. 3 However, under the same conditions arterial relaxant responses to forskolin, an activator of AC, were not significantly different between the WKY and SHR. 4 The relaxant responses due to activation of A 2 ‐adenosine. H 2 ‐histamine and D 1 ‐dopamine receptors were significantly decreased in the SHR arteries. 5 Nitroprusside and nifedipine, agents which are independent of the Gs·AC system, produced similar arterial relaxations in the WKY and SHR. 6 These results support the hypothesis that a reduced function of Gs in the SHR is responsible for the decreased arterial responsiveness to a variety of receptor agonists whose mechanism of action involves AC activation.