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 s tudies have reported that there is a decreased concentration of the in hibitory neurotransmitter, GABA, in the hypothalamus of the SHR. The o bjective of the present study was to assess any variations in GABAergi c modulation of cardiovascular activity in SHRs compared to normotensi ve Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats. Arterial pres sure and heart rate responses to microinjections of the GABA synthesis inhibitor 3-mercaptopropionic acid (3-MP) into the posterior hypothal amic area of anesthetized young (6-8 weeks) and mature (11-16 weeks) h ypertensive and normotensive rats were recorded. Microinjection of 3-M P 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 WK Y, mature SD, young WKY, and young SHR, respectively. In addition, hea rt rate was elevated by 33.2 +/- 21.9 beats/min, 70.0 +/- 25.3 beats/m in, 56.3 +/- 15.0 beats/min and, 45.9 +/- 10 beats/min in the mature W KY, adult SD, young WKY, and young SHR groups, respectively. In contra st, microinjection of 3-MP into the posterior hypothalamus of adult SH Rs produced no significant change in arterial pressure (-5.0 +/- 1.8 m mHg) or heart rate (+5.3 +/- 6.1 beats/min). In three of the adult SHR s, cardiovascular responses to electrical stimulation in the PH were c ompared to responses elicited by microinjection of 3-MP into the same PH site. Electrical stimulation produced large increases in both arter ial pressure and heart rate; however, microinjection of 3-MP produced no significant changes in cardiovascular activity. These results indic ate that spontaneously hypertensive rats have a deficiency in the toni c GABAergic input onto posterior hypothalamic neurons. This alteration may contribute to the maintenance of the elevated blood pressure in s pontaneously hypertensive rats.