Antihypertensive effect of the GABA receptor agonist muscimol in spontaneously hypertensive rats. Role of the sympathoadrenal axis.

Abstract

The antihypertensive action of central GABA-ergic stimulation was investigated in conscious stroke prone spontaneously hypertensive rats. Injection of the potent GABA agonist muscimol (0.01-1 microgram) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 +/- 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of -52.7 +/- 5 mm Hg lasting for about 90 minutes. This was accompanied by bradycardia and sedation. Pretreatment with atropine (2 mg/kg, ip, or 15 micrograms/kg, icv) did not significantly influence the muscimol-induced fall in mean arterial pressure. In normotensive (109.3 +/- 1.9 mm Hg) Wistar-Kyoto controls, the maximal decrease in mean arterial pressure was -12.1 +/- 1.6 mm Hg from 109.3 +/- 1.9 mm Hg, and the duration of the effect was much less than in stroke prone spontaneously hypertensive rats, Following 1 microgram muscimol, icv, plasma noradrenaline did not fall significantly in stroke prone spontaneously hypertensive and Wistar-Kyoto rats, but in stroke prone spontaneously hypertensive rats, plasma adrenaline was fully suppressed (from 118.1 +/- 24.2 to 22.8 +/- 5.7 pg/ml) throughout the depressor response. The efferent sympathetic nervous activity as directly recorded from the n. splanchnicus was similar in conscious stroke prone spontaneously hypertensive and Wistar-Kyoto rats, and was moderately reduced in both strains by 1 microgram muscimol, icv.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of the Hypothalamic Paraventricular Nucleus in Spontaneously Hypertensive Rats Dramatically Reduces Sympathetic Vasomotor Tone

“…This study demonstrates the profound effect of one of these excitatory inputs, under basal conditions, in anesthetized rats. Considerable experimental evidence implicates altered drive to the sympathetic nervous system from the rostral forebrain in the maintenance of several forms of hypertension, including SH, 8,9,20,21 DOCA salt, 22 and renovascular hypertensive 10,[23][24][25] rats. In this study we demonstrate that the response to removal of the PVN excitatory input is more pronounced in the SHR than in the WKY.…”

γ-Aminobutyric Acid (GABA)-A Function and Binding in the Paraventricular Nucleus of the Hypothalamus in Chronic Renal-Wrap Hypertension

“…Intraventricular administration of a GABA agonist causes a decrease in arterial pressure by reducing sympathetic nervous system activity. [21][22][23] Most of the response is the result of a hindbrain action, inasmuch as administration of GABA on the ventral surface of the medulla or into the rostral ventrolateral medulla causes profound depressor responses. 24,25 However, a hypothalamic site of action is suggested by GABAergic inhibition of the central angiotensin response 26 and baroreceptor-mediated vasopressin release.…”

Cardiovascular Effects of Overexpression of Endothelial Nitric Oxide Synthase in the Rostral Ventrolateral Medulla in Stroke-Prone Spontaneously Hypertensive Rats

“…4 It has been shown that spontaneously hypertensive rats (SHR) or stroke-prone SHR (SHRSP) exhibit increased sympathetic activity during development of hypertension and that a positive correlation exists between mean blood pressure and sympathetic nerve activity. [5][6][7][8][9][10] Some studies have also reported that there is a disorder of the L-arginine-NO pathway in SHR and SHRSP. [11][12][13][14] The pressor responses to intravenous administration of the NOS inhibitors N G -nitro-Larginine methyl ester (L-NAME) 11 or N G -monomethyl-Larginine (L-NMMA) 12 have been demonstrated to be smaller in SHR than in WKY.…”