Age-associated decrease in histamine-induced vasodilation may be due to reduction of cyclic GMP formation.
1. The effects of aging on histamine-induced vasodilatation and cyclic GMP production in rat thoracic aorta were investigated. 2. This histamine-induced dilatation of the aorta was mediated by H1-receptors and was dependent on the endothelium. 3. Histamine induced the greatest dilatation of arteries of 3-4 week old rats, progressively less of those of rats of 8 to 56 weeks old, and scarcely detectable dilatation of those of 100 week old rats. 4. Histamine induced cyclic GMP production in aorta from rats of 4 weeks old, with no change in the cyclic AMP level. This increase in the cyclic GMP level induced by histamine also decreased with age, being about 70% as great at 8 weeks, 50% as great at 50-60 weeks, and 10% as great at 130 weeks of age. 5. Removal of the endothelium completely abolished the histamine-induced increase in cyclic GMP. 6. The dilator effect of nitroprusside, which enhances cyclic GMP production by stimulating guanylate cyclase directly (not indirectly via the endothelium derived relaxing factor, EDRF), also showed age-related attenuation. 7. The dilator effect of 8-bromo cyclic GMP, which stimulates cyclic GMP-dependent protein kinase, also decreased during aging. 8. These results suggest that aging reduces the ability of the endothelium to produce EDRF, which stimulates guanylate cyclase, and so decreases cyclic GMP production. Thus the decreased dilator response of the arteries to histamine during aging is probably due to both loss of endothelial function and reduction of guanylate cyclase activity. Alteration of cyclic GMP-dependent protein kinase activity may also participate in the age-related changes.
Moritoki
H
H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Tanioka
A
A
Maeshiba
Y
Y
Iwamoto
T
T
Ishida
Y
Y
Araki
H
H
D000375:Aging / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*
D009599:Nitroprusside; C016276:8-bromocyclic GMP; D006632:Histamine; D000242:Cyclic AMP; D006152:Cyclic GMP