Effects of age and hypertension on endothelium-dependent vasodilating responses.

To investigate whether the release of endothelium-derived relaxing factors (EDRF) was affected during the development of hypertension or by age, male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in the age of 4, 8, 12, 24, 36 or 48 weeks old were used for this study. The thoracic aorta and superior mesenteric arteries of these animals with different ages were excised after general anesthesia. In addition to the measurement of basal EDRF release, vascular responses to acetylcholine (ACh) were assessed with or without the treatment of various inhibitors (such as N omega-nitro-L-arginine, SQ29548 or 3-amino-1,2,4-triazole) to clarify the possible mechanisms for changes of ACh-evoked vasorelaxation. We found that 1) the basal release of EDRF was declined during the development of hypertension, especially in the mesenteric arteries; 2) ACh-induced vasorelaxation in the thoracic aorta was mainly due to the stimulated release of nitric oxide, whereas the effect of endothelium-derived hyperpolarizing factor was more prominent in the mesenteric arteries than in thoracic aortae; 3) high concentrations of ACh stimulated the release of endothelium-derived contracting factors in the thoracic aorta of SHR and WKY of 24 weeks or older, and in the mesenteric arteries of 48-week-old SHR. In conclusion, basal release of EDRF decreases before hypertension is well established, and the impairment of ACh-evoked vasorelaxation in adult SHR is mainly due to the release of contracting factors.