Hemodynamic responses to endothelin-1 and endothelin antagonists microinjected into the nucleus tractus solitarius in...

The role of endothelin-1 (ET-1) within the nucleus tractus solitarius (NTS) in central cardiovascular control was investigated by local microinjections of ET-1 and ET-receptor antagonists. In urethane-anesthetized Sprague-Dawley rats, a unilateral microinjection of ET-1 (1.0, 3.3, and 10.0 pmol) into the NTS significantly increased arterial pressure, left ventricular systolic pressure, and dP/dt(max) in a dose-dependent manner, and slightly decreased heart rate in a dose-independent manner. The pressor effect lasted >90 min. In normotensive rats, neither PD147953, a selective ETA-receptor antagonist, nor PD142893, a mixed ETA- and ETB-receptor antagonist, microinjected into the NTS elicited any changes in arterial pressure or heart rate. The pressor and bradycardic effects evoked by microinjection of ET-1 into the NTS could be blocked by local pretreatment with PD147953 and completely eliminated by intravenous pretreatment with the ganglionic blocker hexamethonium. The arterial baroreflex sensitivity was almost totally suppressed by microinjection of ET-1 (3.3 pmol) in alpha-chloralose-anesthetized Sprague-Dawley rats. A similar pattern of changes in the hemodynamic variables was elicited by microinjection of ET-1 (3.3 pmol) into the NTS in spontaneously hypertensive rats (SHRs) compared with Wistar-Kyoto (WKY) rats. In SHRs, microinjection of PD142893 did not elicit any changes in arterial pressure or heart rate. These results suggest that ET-1 modulates reflex control of hemodynamics by activation of autonomic nerve via ETA receptors in the NTS, and that the responsiveness of SHRs to ET-1 or PD142893 is similar to that of WKY rats.