SUBARACHNOID HEMORRHAGE AND ENDOTHELIAL L-ARGININE PATHWAY IN SMALL BRAIN-STEM ARTERIES IN DOGS

Background and Purpose: Experiments were designed to determine the effect of subarachnoid hemorrhage on endothelium-dependent relaxations in small arteries of the brain stem. A ''double-hemorrhage'' canine model of the disease was used, and the presence of vasospasm in the basilar artery was confirmed by angiography. Methods: Secondary branches of both untreated basilar arteries (inner diameter, 324 +/- 11 mum; n = 12) and arteries exposed to subarachnoid hemorrhage for 7 days (inner diameter, 328 +/- 12 mum; n = 12) were dissected and mounted on glass microcannulas in organ chambers. Changes in the intraluminal diameter of pressurized arteries were measured using a video dimension analyzer. Results: In untreated arteries, 10(-11) to 10(-7) M vasopressin, 10(-10) to 10(-6) M bradykinin, and 10(-9) to 10(-6) M calcium ionophore A23187 caused endothelium-dependent relaxations. At 10(-6) and 3 x 10(-4) M the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) abolished relaxations to vasopressin and produced small but significant rightward shifts of the concentration-response curves to bradykinin and A23187. At 10(-3) M L-arginine prevented the inhibitory effect of L-NAME. Subarachnoid hemorrhage abolished relaxations to vasopressin but did not affect relaxations to bradykinin or A23187. Conclusions: These studies suggest that in small arteries of the brain stem vasopressin causes relaxations by activation of the endothelial L-arginine pathway. This mechanism of relaxation is selectively inhibited by subarachnoid hemorrhage. Preservation of endothelium-dependent relaxations to bradykinin and A23187 is consistent with the concept that small arteries are resistant to vasospasm after subarachnoid hemorrhage.