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Journal of Pharmacology And Experimental Therapeutics, Vol. 191, Issue 1, 147-155, 1974
Copyright © 1974 by American Society for Pharmacology and Experimental Therapeutics

AGE-RELATED CHANGES IN VASCULAR RESPONSIVENESS TO CYCLIC NUCLEOTIDES AND CONTRACTILE AGONISTS

Marlene L. Cohen 1 and Barry A. Berkowitz 1

1 Department of Physiological Chemistry, Roche Institute of Molecular Biology, Nutley, New Jersey

Contraction of spirally cut aortic strips was found to be age dependent. Norepinephrine, serotonin and potassium chloride produced greater maximal tension in aortic strips from 9-to 13-week-old rats as compared to strips from younger (3-5 weeks) rats. This age-related effect also occurred in mesenteric artery strips and may be explained, in part, by an increased amount of muscle in preparations from older rats. Percent relaxation was found to be dependent on the agonist-induced contractile tension, and, therefore, relaxation was examined in preparations contracted to equivalent tensions. Vascular relaxation in response to both cyclic adenosine 3', 5'-monophosphate and dibutyryl cyclic adenosine 3', 5'-monophosphate was decreased with increasing animal age. Cyclic guanosine 3', 5'-monophosphate also relaxed aortic preparations in a similar age-dependent fashion. Decreased vascular responsiveness to cyclic nucleotides with age was mimicked with inhibitors of phosphodiesterase but could not be demonstrated with two other vasodilators, adenosine and nitroglycerin. The specificity of this differential effect for cyclic nucleotides may provide an explanation for the previously observed loss of aortic responsiveness with age to the beta adrenergic stimulant, isoproterenol, and certainly indicates the importance of animal age in studies of the functional effects of cyclic nucleotides.

Submitted on February 2, 1974
Accepted on June 12, 1974




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Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics.