Abnormal renal vascular reactivity to acetylcholine and nitroprusside in aging rats.

1. The actions of acetylcholine (ACh), CaCl2 and nitroprusside (NP) were studied in aortic strips and in the perfused kidneys from adult (4-6 months old) and aging (23-24 months old) rats. 2. ACh and CaCl2 produced a dose-related relaxation in aortic strips from adult and old rats; maximal responses to both vasodilators were significantly reduced (ACh: adult = 66.4 +/- 6.1%, Old = 27.1 +/- 5.7%, P < 0.001; CaCl2: adult = 75.6 +/- 3.9%, Old = 54.1 +/- 4.1%, P < 0.01) in aortas from old rats. NP-evoked relaxation was not significantly different between the two groups. 3. In kidneys from adult rats, ACh produced dose-related decreases in renal perfusion pressure (RPP), whereas, in kidneys from old rats, ACh produced a dose-related decrease at low doses, and biphasic responses (vasodilatation followed by vasoconstriction) at medium to high doses, with a reduced vasodilator component. Vasodilator response to ACh to the highest dose; ACh; adult = 78.7 +/- 2.8%, Old = 40.6 +/- 2.6%, P < 0.001). In kidneys from adult rats, NP produced a dose-related decrease in RPP. However, in kidneys from old rats, NP produced vasoconstriction at low doses, biphasic responses at medium doses (vasoconstriction followed by vasodilation), and vasodilation at the highest dose. 4. The results of the present study demonstrated that: (a) The isolated perfused kidney from aging rats had a dual response (with an important vasoconstrictor component) to ACh and NP, which may be due to the release of a nonprostanoid vasoconstrictor or to abnormalities in the renal vascular smooth muscle. In contrast, in aortic-strips from old and adult rats, these agents only caused relaxation; (b) aging is accompanied by reduced endothelium-dependent relaxation both in large arteries and in resistance vessels; and (c) large arteries from aging rats require a higher concentration of extracellular calcium to stabilize the membrane of smooth muscle cells.