We assessed the relative contributions of endothelium-derived relaxing factors to renal vasodilation in vivo and determined whether these are altered in established streptozotocin-induced diabetes. In non-diabetic rats, stimulation of the endothelium by locally administered acetylcholine or bradykinin induced transient renal hyperemia. Neither basal renal blood flow (RBF) nor renal hyperemic responses to acetylcholine or bradykinin were altered by blockade of prostanoid production (indomethacin), or by administration of charybdotoxin (ChTx) plus apamin to block endothelium-derived hyperpolarizing factor (EDHF). In contrast, combined blockade of nitric oxide (NO) synthase (N(omega)-nitro- L-arginine methylester; L-NAME) and prostanoid production reduced basal RBF and the duration of the hyperemic responses to acetylcholine and bradykinin, and revealed a delayed ischemic response to acetylcholine. Accordingly, L-NAME and indomethacin markedly reduced integrated (area under the curve) hyperemic responses to acetylcholine and bradykinin. Peak increases in RBF in response to acetylcholine and bradykinin were not reduced by L-NAME and indomethacin, but were reduced by subsequent blockade of EDHF. L-NAME plus indomethacin and ChTx plus apamin altered RBF responses to endothelium stimulation in a qualitatively similar fashion in diabetic and non-diabetic rats. The integrated renal hyperemic responses to acetylcholine and bradykinin were blunted in diabetes, due to a diminished contribution of the component abolished by L-NAME plus indomethacin. We conclude that NO dominates integrated hyperemic responses to acetylcholine and bradykinin in the rat kidney in vivo. After prior inhibition of NO synthase, EDHF mediates transient renal vasodilation in vivo. Renal endothelium-dependent vasodilation is diminished in diabetes due to impaired NO function. Key words: kidney circulation, acetylcholine, bradykinin, endothelium-derived hyperpolarizing factor, nitric oxide.
|Pages (from-to)||R829 - R839|
|Number of pages||11|
|Journal||American Journal of Physiology - Regulatory Integrative and Comparative Physiology|
|Publication status||Published - 2008|
Edgley, A. J., Tare, M., Evans, R. G., Skordilis, C., & Parkington, H. C. (2008). In vivo regulation of endothelium-dependent vasodilation in the rat renal circulation and the effect of streptozotocin-induced diabetes. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 295(3), R829 - R839.