Vascular reactivity of isolated perfused kidneys from male and female spontaneously hypertensive rats.

We investigated vascular reactivity in isolated, Tyrode perfused kidneys from male (blood pressure, 222.6 mm Hg) and female (blood pressure, 178.5 mm Hg) spontaneously hypertensive rats (SHR, 4-6 months age) and sex and weight matched normotensive Kyoto Wistar and Wistar control rats. Optimal perfusion flows and basal pressures were similar in sex-matched SHR and control rats. Subraaximal constrictor responses to renal nerve stimulation were normal in SHR kidneys, but responses to exogenous norepinephrine were greater than control. Cocaine potentiated nerve stimulation responses more in SHR than control kidneys, while exogenous norepinephrine responses were potentiated to a similar extent. Dose-response curves in SHR kidneys were to the left of control with the following order of shift magnitude; 5-hydroxytryptamine > angiotensin II > norepinephrine > barium. In SHR kidneys, the ED20 (dose of agonist that evoked a 20% maximal response) for norepinephrine, 5-hydroxytryptamine, and angiotensin, but not for barium, was significantly lower than control; response duration was normal for norepinephrine and 5-hydroxytryptamine but prolonged for barium and angiotensin. SHR kidneys developed 5hydroxytryptamine tachyphylaxis more slowly than control. Dose-response curve shifts were greater in kidneys from male than female SHR, maximal responses were always increased in the former, but only for 5-hydroxytryptamine and angiotensin in the latter. These results indicate that in the SHR kidney (1) structural vascular changes may contribute to hyperreactivity in the male; (2) renal vessels of male and female SHR are supersensitive to receptorstimulating agonists and exhibit impaired relaxation; (3) normal nerve stimulation response amplitude is due to a more efficient, cocaine sensitive, neurotransmitter disposition masking increased norepinephrine sensitivity; and (4) the large increase in 5-hydroxytryptamine reactivity is partly due to attenuated tachyphylaxis.