Differential regulation of ANF-R2 receptors coupled to adenylyl cyclase in cardiovascular tissues in hypertension.
We have recently shown that ANF-R2 receptors are coupled to the adenylyl cyclase/cAMP system through inhibitory guanine nucleotide regulatory protein (Gi). The present studies were undertaken to investigate the regulation of ANF-R2 receptor-mediated inhibition of adenylyl cyclase in spontaneously hypertensive rats (SHR) which have been reported to have high plasma ANF levels. ANF99-126 inhibited adenylyl cyclase activity in a concentration dependent manner in both aorta and heart sarcolemma from SHR and age-matched Wistar-Kyoto (WKY) rats, however, the extent of inhibition was greater in SHR as compared to WKY. On the other hand, ANF99-126 also inhibited the adenylyl cyclase activity in rat platelets from WKY rats in a concentration dependent manner, however, the inhibition in SHR was completely attenuated. In addition GTP gamma S stimulated adenylyl cyclase activity by about 600% in aorta from WKY rats and about 300% in SHR. On the other hand, the GTP gamma S-stimulated adenylyl cyclase activity was higher in platelets from SHR as compared to WKY. The observed difference may be attributed to the differential alterations in ANF-R2 receptor number or postreceptor events or both. Nonetheless, these results indicate that ANF-R2 receptors in platelets from SHR are differentially regulated than those in heart and aorta.
Anand-Srivastava
M B
MB
Department of Physiology, Faculty of Medicine, University of Montréal, Québec, Canada.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000648:ultrastructure; D009320:Atrial Natriuretic Factor / Q000097:blood; D001792:Blood Platelets / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006973:Hypertension / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D009206:Myocardium / Q000737:chemistry / Q000648:ultrastructure; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017461:Receptors, Atrial Natriuretic Factor / Q000032:analysis / Q000502:physiology*; D012508:Sarcolemma / Q000201:enzymology / Q000502:physiology
D000067956:Adenylyl Cyclase Inhibitors; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009320:Atrial Natriuretic Factor; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D017461:Receptors, Atrial Natriuretic Factor