Cardiac norepinephrine, beta-adrenoceptors, and Gi alpha-proteins in prehypertensive and hypertensive spontaneously hypertensive rats.
In spontaneously hypertensive rats (SHR), cardiac adenylate cyclase is desensitized owing to down-regulation of myocardial beta-adrenoceptors and an increase in Gi alpha. We wished to determine whether these biochemical alterations in the beta-adrenoceptor-adenylate cyclase system precede development of hypertensive cardiac hypertrophy or whether this increase occurs only in later stages of the syndrome and represents a secondary phenomenon. Myocardial samples from 5- and 13-week-old SHR and age-matched Wistar Kyoto rats (WKY) as controls were studied. Cardiac beta-adrenoceptors were studied with [125I]cyanopindolol ([125I]ICYP] as radiolabeled ligand. beta-Adrenoceptor subtypes were determined with the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively. Gi alpha proteins were measured with the pertussis toxin-catalysed [32P]ADP ribosylation. Myocardial norepinephrine (NE) content was investigated with high pressure liquid chromatography. In myocardial membranes of 13-week-old SHR, the number of total beta-adrenoceptors as well as beta 1- and beta 2-adrenoceptors was reduced. No difference was observed between SHR and WKY, at age 5 weeks. The nonionic detergent Lubrol PX at 0.5% (vol/vol) increased the amount of detectable Gi alpha by a factor of 14. Under these optimal conditions, Gi alpha was increased by 30% in 13-week-old SHR, but not 5-week-old SHR as compared with WKY. Myocardial NE content was increased by 25-35% in both 5- and 13-week-old SHR as compared with WKY. The results showed that nonspecific beta-adrenoceptor downregulation and an increase in Gi alpha occurs in hypertensive cardiac hypertrophy of SHR. In the prehypertensive stage, these changes were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Böhm
M
M
Klinik III für Innere Medizin der Universität zu Köln, Germany.
Castellano
M
M
Paul
M
M
Erdmann
E
E
D000244:Adenosine Diphosphate / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000032:analysis*; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000737:chemistry*; D009638:Norepinephrine / Q000032:analysis*; D037342:Pertussis Toxin; D010761:Phosphorus Radioisotopes; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D012266:Ribose / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010761:Phosphorus Radioisotopes; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D000244:Adenosine Diphosphate; D012266:Ribose; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009638:Norepinephrine