Excessive salt or cholesterol intake alters the balance among endothelium-derived factors released from renal arteries in spontaneously hypertensive rats

We investigated the vasorelaxation in renal arteries isolated from spontane ously hypertensive rats (SHRs) fed a basal, a high-sail, or a high-choleste rol diet for 8 weeks. In renal arterial rings from the control group, acety lcholine (ACh)-induced endothelium-dependent relaxations were markedly incr eased by indomethacin (IND) and ONO-3708, a prostaglandin H-2/thromboxane A (2)-receptor antagonist, but not affected by OKY-046, a thromboxane A, synt hetase inhibitor. These increased relaxations were partially inhibited by e ither NG-nitro-L-arginine methyl ester (L-NAME) or charybdotoxin (CTX), and almost completely abolished by the combination of L-NAME plus CTX. The ACh -induced endothelium-dependent relaxations in the absence of IND were signi ficantly attenuated by the high-salt intake but not affected by the high-ch olesterol intake. The degrees of relaxations in the presence of IND were ap proximately equal among the three diet groups. On the other hand, the relax ations in the presence of IND plus L-NAME were significantly augmented by a high-cholesterol intake and abolished by a high-salt intake, and the relax ations in the presence of IND plus CTX were slightly reduced by a high-chol esterol intake and significantly augmented by a high-salt intake. The produ ction of cyclic guanosine monophosphate (cGMP) in response to ACh was signi ficantly decreased by a high-cholesterol intake and tended to be increased by a high-salt intake. These findings indicate that in the renal artery of SHRs, ACh causes production of a sufficient amount of nitric oxide (NO), to gether with a relaxing factor resembling endothelium-derived hyperpolarizin g factors (EDHFs) and also endothelium-derived contracting factors (EDCFs), probably prostaglandin H-2. Our results also suggest that excessive salt i ntake increases the release of EDCF and NO and decreases that of an EDHF-li ke factor, whereas excessive cholesterol intake increases release of an EDH F-like factor and decreases that of NO.