Endothelium‐derived relaxing, contracting and hyperpolarizing factors of mesenteric arteries of hypertensive and normotensive rats

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Abstract
Differences in the acetylcholine (ACh)‐induced endothelium‐dependent relaxation and hyperpolarization of the mesenteric arteries of Wistar Kyoto rats (WKY) and stroke‐prone spontaneously hypertensive rats (SHRSP) were studied. Relaxation was impaired in preparations from SHRSP and tendency to reverse the relaxation was observed at high concentrations of ACh in these preparations. Relaxation was partly blocked by NG‐nitro‐L‐arginine (L‐NOARG, 100 μM) and, in the presence of L‐NOARG, tendency to reverse the relaxation was observed in response to higher concentrations of ACh, even in preparations from WKY. The relaxation remaining in the presence of L‐NOARG was also smaller in preparations from SHRSP. The tendency to reverse the relaxation observed at higher concentrations of ACh in preparations from SHRSP or WKY in the presence of L‐NOARG were abolished by indomethacin (10 μM). Elevating the K+ concentration of the incubation medium decreased relaxation in the presence of both indomethacin and L‐NOARG. Relaxation in the presence of L‐NOARG and indomethacin was reduced by the application of both apamin (5 μM) and charybdotoxin (0.1 μM). This suggests that the relaxation induced by ACh is brought about by both endothelium‐derived relaxing factor (EDRF, nitric oxide (NO)) and hyperpolarizing factor (EDHF), which activates Ca2+‐sensitive K+ channels. Electrophysiological measurement revealed that ACh induced endothelium‐dependent hyperpolarization of the smooth muscle of both preparations in the presence of L‐NOARG and indomethacin; the hyperpolarization being smaller in the preparation from SHRSP than that from WKY. These results suggest that the release of both NO and EDHF is reduced in preparations from SHRSP. In addition, indomethacin‐sensitive endothelium‐derived contracting factor (EDCF) is released from both preparations; the release being increased in preparations from SHRSP. British Journal of Pharmacology (1999) 126, 709–716; doi:10.1038/sj.bjp.0702355