DISINHIBITION OF THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS INCREASES MEAN CIRCULATORY FILLING PRESSURE IN CONSCIOUS RATS

Venous capacitance plays an important role in the control of cardiac o utput. However, the central nervous system sites and neurochemical sig nals involved in modulating venous function remain to be fully elucida ted. The hypothalamic paraventricular nucleus (PVN) is an important si te modulating autonomic outflow to the cardiovascular system. The pres ent study tested the hypothesis that removal of tonic GABAergic tone i n the PVN would increase peripheral venous tone. Mean circulatory fill ing pressure was used as an index of venous tone. Arterial pressure, v enous pressure, heart rate, and mean circulatory filling pressure (MCF P) were monitored in conscious male Sprague Dawley rats. The rats were challenged with microinjections of bicuculline methiodide (BMI) (25 n g) or vehicle (artificial cerebrospinal fluid) into the PVN. In one gr oup of rats, BMI injections were performed before and after ganglionic blockade with chlorisondamine hydrochloride (10 mg/kg) and atropine ( 0.4 mg/kg) given subcutaneously. In a second group, BMI injections wer e performed in chlorisondamine-treated rats whose blood pressure had b een returned to control with an infusion of norepinephrine. Injection of bicuculline into the PVN increased MAP (14 +/- 2 to 18 +/- 2 mmHg) and HR (49 +/- 12 to 74 +/- 14 bpm). MCFP also increased significantly by 1.00 +/- 0.17 to 1.39 +/- 0.18 mmHg, indicating an increase in the driving pressure for venous return. Injection of the vehicle did not affect these variables. In both groups, ganglionic blockade significan tly attenuated the bicuculline-induced increases in MAP, HR and MCFP. These data indicate that sympathetic drive from the PVN to the venous system is under tonic GABAergic control.