Vasodilator responses in perfused rabbit kidney: the role of endothelium.

The responses to vasodilator agents of renal vasculature were studied in perfused rabbit kidney. Acetylcholine (ACh) and calcium-ionophore (A23187), as endothelium-dependent relaxing agents, and prostacyclin (PGI2), an endothelium-independent vasodilator, induced a rapid and reversible fall in perfusion pressure of the noradrenaline (NA) constricted renal vasculature. The vasodilator responses of the preparations were not lost after perfusing the kidney with hypotonic Krebs-solution or 10 mumol/l mepacrine. Collagenase treatment significantly reduced the vasodilator responses, not only to ACh and A23187, but also to PGI2. Perfusion of the renal vascular bed with dexamethason did not influence the vasodilator responses. Exposure of the renal vasculature to p-bromophenacylbromide (PBPB), which is a known inhibitor of phospholipases, markedly reduced the ACh- and A23187-induced vasodilatation. The responses to PGI2, however, were also moderately depressed in the presence of PBPB. The lipoxygenase-inhibitor nordihydroguaiaretic acid (NDGA), inhibited the responses to ACh and A23187, but did not reduce the responses to PGI2. Some commonly used methods and chemicals, that have been successful in destroying the endothelium of large vessels, were not effective in renal vasculature. We failed to demonstrate that the inhibitory actions of these treatments were specific for the endothelium-dependent responses. Our results provide indirect evidence for the involvement of lipoxygenase products in the vasodilatation responses of the rabbit kidney and for a possible role of endothelium in the reactivity of renal vasculature.