Effect of age and spontaneous hypertension on the tachyphylaxis to 5-hydroxytryptamine and angiotensin II in the isolated rat kidney.

The isolated and perfused kidney of the mature spontaneously hypertensive rat (SHR) exhibits an increased vascular reactivity and a delayed tachyphylaxis to 5-hydroxytryptamine, when compared to weight-matched normotensive animals. To evaluate the influence of the duration of the hypertensive state on these differences, the vascular reactivity to 5-hydroxytryptamine was determined in isolated kidneys from age-matched normotensive and spontaneously hypertensive rats of 3.5, 6 and 12 months of age. Responses to increasing doses of 5-hydroxytryptamine were compared. At all ages the responses to the agonist were greater in the SHR than in the control rats. In the normotensive rats, the sensitivity to the monoamine decreased, while the maximal response increased with aging. The vascular reactivity to increasing doses of 5-hydroxytryptamine was not altered by aging in the SHR. There was a significant correlation between the maximal vasoconstrictor response to 5-hydroxytryptamine in the isolated kidneys and the systolic arterial blood pressure (SBP) of the donor rats. Maximal constrictor responses to 5-hydroxytryptamine were repeated at given intervals. The degree of tachyphylaxis was decreased in hypertensive rats compared with normotensive rats at 3.5, and 6 months age. Tachyphylaxis to 5-hydroxytryptamine was depressed by aging in both normotensive and hypertensive rats. By contrast, tachyphylaxis to angiotensin II (AII) was not effected by either age or hypertension. There was no cross-tachyphylaxis between 5-hydroxytryptamine and AII. Lowering the Ca2+-concentration of the perfusate did not affect tachyphylaxis to either 5-hydroxytryptamine or AII. The present experiments indicate that the delayed tachyphylaxis to 5-hydroxytryptamine in the kidneys of SHR is due to a specific alteration of th vascular smooth muscle cells, which may be the consequence of premature aging.