Differences in responses to norepinephrine and adenosine triphosphate in isolated, perfused mesenteric vascular beds...

The responses to norepinephrine and adenosine 5' triphosphate (ATP) of isolated, perfused mesenteric vascular beds were compared between spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Norepinephrine (0.01-100 nmol) dose-dependently increased perfusion pressure in the intact bed and the arteries, but not in the veins. The maximal responses in SHRs were larger than those in WKY rats. ATP (0.1-3,000 nmol) increased perfusion pressure in all preparations. The responses of the intact bed and the veins were larger in SHRs, whereas there was no strain difference in the arteries. Indomethacin (5 x 10(-6) M) enlarged the norepinephrine responses of both strains only in the intact beds and did not affect the ATP responses, except the veins in SHRs, where it was reduced. N(G)-nitro-L-arginine methyl ester (5 x 10(-6) M), in combination with indomethacin, potentiated the responses, except the arterial response to high doses of norepinephrine in SHRs, which was not affected. Endothelium denudation in the arteries produced similar changes to those after the combined treatment. UK14,304-induced and ADPbetaS-induced decreases in perfusion pressure at increased tone were similar between the strains. Thus neither the vasodilation induced by the stimulation of alpha2-adrenoceptors nor of P2y receptors seems to affect the response to norepinephrine or to ATP, respectively. These results demonstrate that the intact mesenteric vascular bed of SHRs shows potentiated responses not only to norepinephrine, but also to ATP, as compared with WKY rats, and that the critical regions for determining the strain differences for norepinephrine are overall arteries, and that for ATP are the vessels downstream from arterioles. In the intact beds, neither regulation by endogenous prostanoids nor that by endothelium-derived relaxing factors (EDRFs) is implicated in the strain difference. However, these two types of regulation differ markedly between different kinds of vessels.