caa a22 4500 477119980 CHVBK 20180405111634.0 cr unu---uuuuu 170330e19960401xx s 000 0 eng 10.1007/BF00227895 doi (NATIONALLICENCE)springer-10.1007/BF00227895 Anand-Srivastava Madhu Department of Physiology and Groupe de recherche sur le système nerveux autonome, Faculty of Medicine, University of Montreal, H3C 3JC, Montreal, (Quebec), Canada aut G-proteins and adenylyl cyclase signalling in hypertension [Elektronische Daten] [Madhu Anand-Srivastava] The present studies were undertaken to examine if adenylyl cyclase activity and the levels of G-proteins (Gsα and Giα) are altered in cardiovascular tissues in hypertension. Adenylyl cyclase activity and its responsiveness to stimulatory and inhibitory hormones as well as the expression of G-proteins (Gs and Gi) were determined at protein and mRNA levels by using specific antibodies and cDNA probes in hearts and aorta from 12 week old spontaneously hypertensive rats (SHR) and their age-matched control Wistar Kyoto (WKY) rats. The stimulatory effects of guanine nucleotides, isoproterenol, glucagon etc. on adenylyl cyclase activity were decreased in SHR rats as compared to the WKY rats, whereas, the inhibitory hormones inhibited enzyme activity to a grater extent in SHR rats as compared to WKY rats. Furthermore, the levels of Giα-2 and Giα-3 proteins and Giα-2 and Giα-3 mRNA as determined by immunoblotting and Northern blotting techniques respectively were higher in SHR as compared to WKY rats. However, the levels of Gsa were unaltered in SHR. To further investigate if these alterations are the cause or effect of hypertension, the SHRs at various ages of the development of blood pressure (3-5 days, 2, 4 and 8 weeks) and their age-matched WKY were used for G-protein expression and adenylyl cyclase activity. The increased expression of Giα−2 and Giα−3 protein and mRNA levels in hearts and aorta were observed as early as in 2-weeks old SHR as compared to WKY, when the blood pressure was still normal. However, the levels of Gsα in SHR were not different from WKY rats. In addition, the altered responsiveness of adenylyl cyclase to hormone stimulation and inhibition was also observed as early as in 2 week old SHR. These results suggest that the increased expression of Giα−2 and Giα−3 and decreased levels of cAMP precedes the development of blood pressure and may be one of the contributing factors in the pathogenesis of hypertension. Kluwer Academic Publishers, 1996 G-proteins nationallicence adenylyl cyclase nationallicence heart nationallicence aorta nationallicence spontaneously hypertensive rats nationallicence NECA : N-ethylcarboxamideadenosine nationallicence Iso : Isoproterenol nationallicence Glu : Glucagon nationallicence ANF : atrial natriuretic factor nationallicence AII : angiotensin II nationallicence PT : pertussis toxin nationallicence CT : cholera toxin nationallicence FSK : forskolin nationallicence GTPγS : guanosine 5′-[γ-thio]triphosphate nationallicence Gs : stimulatory guanine nucleotide regulatory protein nationallicence Gi : inhibitory guanine nucleotide regulatory protein nationallicence WKY : WistarKyoto rats nationallicence SHR : spontaneously hypertensive rats nationallicence Molecular and Cellular Biochemistry Kluwer Academic Publishers 157/1-2(1996-04-01), 163-170 0300-8177 157:1-2<163 1996 157 11010 https://doi.org/10.1007/BF00227895 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00227895 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Anand-Srivastava Madhu Department of Physiology and Groupe de recherche sur le système nerveux autonome, Faculty of Medicine, University of Montreal, H3C 3JC, Montreal, (Quebec), Canada aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers 157/1-2(1996-04-01), 163-170 0300-8177 157:1-2<163 1996 157 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer