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(Hypertension. 1999;33:530-536.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Enhanced -Aminobutyric Acid–B Receptor Agonist Responses and mRNA Within the Nucleus of the Solitary Tract in Hypertension

Vijayender Rao Durgam; Melissa Vitela; Steven W. Mifflin

From the Department of Pharmacology, The University of Texas Health Science Center at San Antonio.

Correspondence to Vijayender R. Durgam, PhD, Department of Pharmacology, The University of Texas Health Science Center, 7703 Floyd Curl Dr, San Antonio, TX 78284-7764. E-mail durgam{at}uthscsa.edu

Abstract—-Aminobutyric acid–B (GABA_B) receptor function and regulation in the nucleus of the solitary tract (NTS) was examined in Sprague-Dawley rats made chronically (4 to 5 weeks) hypertensive with the one-kidney, figure-8 renal wrap model of hypertension. NTS microinjection of the GABA_B agonist baclofen produced a pressor response that was enhanced in hypertensive rats compared with the response observed in sham-operated normotensive rats (36±4 mm Hg increase in mean arterial pressure in 8 hypertensive rats compared with 21±2 mm Hg increase in 7 sham-operated normotensive rats, P=0.03). Responses to microinjection of GABA_B antagonists (CGP-55845A and SCH-90511), the GABA_A agonist muscimol, the GABA_A antagonist bicuculline, and the GABA reuptake inhibitor nipecotic acid were not different comparing normotensive sham-operated and hypertensive rats. Renal sympathetic nerve responses to NTS microinjection of these drugs were not different in hypertensive compared with normotensive rats. Micropunches of the NTS were homogenized and reverse transcriptase–polymerase chain reaction was performed to examine mRNA levels for the GABA_B receptor. There was a 3-fold increase in GABA_B receptor mRNA levels in the caudal NTS of 7 chronically hypertensive rats compared with levels measured in 8 sham-operated normotensive rats (P=0.01). In conclusion, chronic hypertension is associated with an upregulation of GABA_B receptor function; however, the tonic activity of the system does not appear to be different between normotensive and hypertensive rats. The upregulation of GABA_B receptor function might be due to an increased number of receptors, as suggested by the elevated levels of GABA_B receptor mRNA measured in the NTS of hypertensive rats. All of these alterations suggest that hypertension is associated with dynamic changes in receptor-mediated mechanisms within the NTS, and these alterations could modify baroreflex regulation of cardiovascular function in hypertension.

Key Words: kidney • tractus solitarius • hypertension, renal • receptors, aminobutyric acid • baclofen • reverse transcriptase

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