Studies on the mechanism of the central antihypertensive effect of guanabenz and clonidine.

Mean arterial pressure and heart rate responses were measured following intracerebroventricular (i.c.v.) injections of guanabenz and clonidine in conscious intact, sinoaortic baroreceptor denervated (SAD) animals, and in SAD animals with anteroventral third ventricle (AV3V) or sham-AV3V lesions. These results suggest that in the conscious unrestrained rat: (1) the centrally-mediated depressor effect of guanabenz and clonidine is masked by intact baroreceptors; (2) the centrally mediated bradycardia is independent of baroreceptor function and (3) the integrity of the AV3V region is not required for expression of these central effects.

Role of periaqueductal gray in the pressor response produced by central injections of angiotensin II.

The present studies were undertaken to determine the role of rostral periaqueductal gray (PAG) in mediating the pressor effect produced by intracerebroventricular (icv) injection of angiotensin II (ANG II, 200 ng). Two functionally and anatomically distinct sites were identified in rostral PAG: a dorsomedial site involved in the hemodynamic responses produced by electrical stimulation of the anteroventral third ventricle (AV3V) region and a ventromedial site required for the pressor response elicited by icv administration of ANG II. In Saffan-anesthetized rats, injection of lidocaine (LIDO, 4%) in dorsomedial PAG, but not in ventromedial PAG, significantly attenuated the decrease in hindquarter resistance (HQR) produced by electrical stimulation of the AV3V region, and the poststimulatory increase in mean arterial pressure (MAP) and HQR. The injection of LIDO in ventromedial PAG had no effect on the hemodynamic responses produced by electrical stimulation of the AV3V region in anesthetized rats but significantly attenuated the pressor response produced by icv administration of ANG II in conscious rats. The hypothesis that these two sites receive separate projections was addressed by microinjecting two retrogradely transported fluorescent dyes, Fluoro-Gold and Fast Blue. The anatomic findings suggest that separation of the pathways activated by electrical and chemical stimulation of the AV3V region occurs at the level of rostral PAG.