CARDIOVASCULAR-RESPONSES TO BLOCKADE OF GABA SYNTHESIS IN THE HYPOTHALAMUS OF THE SPONTANEOUSLY HYPERTENSIVE RAT

Previous studies have suggested that a decreased inhibitory input onto neurons within the posterior hypothalamus (PH), a known pressor area, may contribute to hypertension in the spontaneously hypertensive rat (SHR). Recent experiments from this laboratory have shown that neurons in the PH of the SHR have an altered and elevated discharge frequency compared to those in the normotensive rat. In addition, biochemical studies have reported that there is a decreased concentration of the inhibitory neurotransmitter, GABA, in the hypothalamus of the SHR. The objective of the present study was to assess any variations in GABAergic modulation of cardiovascular activity in SHRs compared to normotensive Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats. Arterial pressure and heart rate responses to microinjections of the GABA synthesis inhibitor 3-mercaptopropionic acid (3-MP) into the posterior hypothalamic area of anesthetized young (6-8 weeks) and mature (11-16 weeks) hypertensive and normotensive rats were recorded. Microinjection of 3-MP elicited increases in arterial pressure of 17.4 +/- 3.9 mmHg, 18.1 +/- 7.8 mmHg, 16.9 +/- 6.4 mmHg, and 10.4 +/- 3.5 mmHg in the mature WKY, mature SD, young WKY, and young SHR, respectively. In addition, heart rate was elevated by 33.2 +/- 21.9 beats/min, 70.0 +/- 25.3 beats/min, 56.3 +/- 15.0 beats/min and, 45.9 +/- 10 beats/min in the mature WKY, adult SD, young WKY, and young SHR groups, respectively. In contrast, microinjection of 3-MP into the posterior hypothalamus of adult SHRs produced no significant change in arterial pressure (-5.0 +/- 1.8 mmHg) or heart rate (+5.3 +/- 6.1 beats/min). In three of the adult SHRs, cardiovascular responses to electrical stimulation in the PH were compared to responses elicited by microinjection of 3-MP into the same PH site. Electrical stimulation produced large increases in both arterial pressure and heart rate; however, microinjection of 3-MP produced no significant changes in cardiovascular activity. These results indicate that spontaneously hypertensive rats have a deficiency in the tonic GABAergic input onto posterior hypothalamic neurons. This alteration may contribute to the maintenance of the elevated blood pressure in spontaneously hypertensive rats.