Age-related changes in adenosine and beta-adrenoceptor responsiveness of vascular smooth muscle in man.
1. Ageing is associated with a decline in beta-adrenergic responsiveness in several tissues. Reduced beta-adrenoceptor mediated smooth muscle relaxation in aged man has been demonstrated using the dorsal hand vein technique. Isoprenaline and adenosine activate adenylate cyclase through separate membrane bound receptors to induce vasodilatation. 2. To determine the specificity of reduced beta-adrenergic responsiveness in smooth muscle of aged man, and possible sites of the defect responsible, venodilatory responses to isoprenaline, a beta-adrenoceptor agonist and adenosine were determined in nine young (age 26 +/- 3 years: mean +/- s.d.) and eight elderly (age 70 +/- 5 years), healthy male volunteers. Veins were partially constricted with the alpha 1-adrenoceptor agonist phenylephrine and increasing doses of adenosine (5 to 1220 micrograms min-1) or isoprenaline (271 ng min-1) were infused. 3. Maximal dilatation induced by isoprenaline was 83 +/- 26% in the young and 51 +/- 34% in the elderly, P = 0.02. Maximal dilatation induced at the highest dose of adenosine (1220 micrograms min-1) was similar in young and elderly: 79 +/- 25% vs 88 +/- 28%, P = 0.26. 4. Adenosine venodilatation was measured before and after infusions of theophylline (6.8 to 135 micrograms min-1) for 30 min in six subjects. Adenosine responsiveness was unchanged following theophylline: 48 +/- 16% to 49 +/- 40%, P = 0.44. 5. The results suggest that the age-associated reduced responsiveness of the beta-adrenergic system in human vascular smooth muscle is not shared by venodilatation mediated by adenosine.
Ford
G A
GA
Department of Medicine, Stanford University School of Medicine, CA 94305-5113.
Hoffman
B B
BB
Vestal
R E
RE
Blaschke
T F
TF
D000241:Adenosine / Q000494:pharmacology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000628:Aminophylline / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D000628:Aminophylline; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol