Central effects of endothelin on baroreflex of spontaneously hypertensive rats

Abstract

To study the contribution made by central endothelin to cardiovascular regulation in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls. Central endothelin binding was measured with receptor autoradiography. The baroreceptor heart rate reflex was measured by sigmoidal curve-fitting of the mean arterial pressure and heart rate responses evoked by alternating intravenous injections of nitroprusside or phenylephrine. The baroreflex gain was derived as a function of the heart rate range and the curvature coefficient. Autoradiographic experiments with [125I]-endothelin-1 showed low to moderate binding in various medullary nuclei involved in cardiovascular regulation, such as the nucleus tractus solitarius and the ventrolateral medulla. A moderate binding density was found in regions such as the hypoglossal nucleus and the spinal trigeminal nucleus, whereas a high binding density was observed in the molecular layer of the cerebellum. The binding density was significantly lower in the ventrolateral medulla of SHR than in that of WKY rats, but there were no differences in other medullary regions. Compared with WKY rats, the SHR had higher mean arterial pressures and heart rates but tended to have a reduced baroreceptor heart rate reflex gain. This latter change was entirely attributed to a significantly lower heart rate range, caused by an elevated lower heart rate plateau in SHR. The intracisternal injection of endothelin-1 at 25 pmol/kg did not influence the resting mean arterial pressure or heart rate, but it caused a significant increase in baroreflex gain, in both SHR and WKY rats. The extent of the effect was similar in the two strains and was attributed to a significant increase in the curvature coefficient of the sigmoidal baroreflex curve. Consequently, the range over which blood pressure changes evoked reflex changes in the heart rate was reduced by endothelin-1 treatment in both SHR and WKY rats. The heart rate range was not affected and remained different between SHR and WKY rats after the endothelin-1 injection. The intracisternal injection of endothelin-3 at 25 pmol/kg, but not at 2.5 pmol/kg, had effects similar to those of endothelin-1 on the baroreflex. These results show that binding sites for endothelin-1 are present in various regions of the hindbrain of SHR and WKY rats and that central administration of endothelin-1 sensitizes the baroreceptor heart rate reflex. However, this latter effect is similar in SHR and WKY rats and is mediated by a mechanism which is distinct from that underlying the difference in reflex sensitivity between these strains.