Central GABAergic Mechanisms Are Defective in Salt-Induced Hypertension in Borderline Hypertensive Rats

Abstract

We examined the role of central GABAergic mechanisms in salt-induced hypertension and exaggerated responses to stress in borderline hypertensive rats (BHR), the first offspring of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The studies were done in conscious BHR and WKY on high (H) (8% NaCl) or normal (N) (0.3% NaCl) salt diets for 5 weeks. A high-salt diet elevated arterial pressure (AP) (p<0.01) and augmented pressor responses to shaker stress (p<0.05) in BHR but not in WKY. Intravenous hexamethonium caused a greater decrease in AP in BHR-H than in BHR-N at rest. Muscimol (a GABA agonist) injected into the central ventricle (icv) caused a greater decrease in resting AP (p<0.01) and heart rate (HR) (p<0.05) in BHR-H than in BHR-N. Renal sympathetic nerve activity (RSNA) did not change in BHR-H, but increased (p<0.05) in BHR-N during muscimol-induced hypotension, although the magnitudes of muscimol-induced hypotension were greater in BHR-H than in BHR-N. The increases in RSNA in response to intravenous nitroglycerin were similar in BHR-H and BHR-N. Muscimol attenuated pressor and tachycardic responses to stress more in BHR-H than in BHR-N (p<0.01). Muscimol did not alter AP and HR at rest or their responses to stress in the two groups of WKY. The magnitudes of pressor response to bicuculline (a GABA antagonist) did not differ between the two groups of BHR. These results suggest that a high salt diet may alter the central GABAergic system in BHR, which contributes to salt-induced hypertension and augmented pressor and tachycardic responses to stress. (Hypertens Res 1995; 18: 285-293)