GABA_A receptor activation at medullary sympathetic neurons contributes to postexercise hypotension

Abstract

A single bout of exercise results in a postexercise hypotension (PEH) that is accompanied by a reduced baroreflex function. Based on the role of rostral ventrolateral medulla (RVLM) neurons in controlling sympathetic nerve activity (SNA) and blood pressure, the role of gamma-aminobutyric acid (GABA) in controlling RVLM neuronal activity, and the reduced baroreflex-SNA relationship during PEH, we determined whether: 1) RVLM neuronal activity is decreased during PEH, 2) GABA(A)-receptor mechanisms mediate the decrease, and 3) baroreflex control of RVLM activity is reduced. Spontaneously hypertensive rats (SHR) were subjected to 40 min of treadmill or sham exercise (Sham PEH). PEH lasted 10 h in conscious and anesthetized SHR, indicating that the anesthetics did not affect the expression of PEH. Extracellular RVLM neuronal activity having a cardiac and sympathetic rhythm, lumbar SNA, and blood pressure were recorded at rest and during baroreflex function curves. Resting RVLM neuronal activity was lower and was increased to a greater extent by GABA(A)-receptor antagonism in PEH versus Sham PEH (P < 0.05). Baroreflex control of RVLM neuronal activity operated with a reduced gain (P < 0.05). Thus increased GABA signaling at RVLM neurons may contribute to PEH.

Mechanism behind Augmentation in Baroreflex Sensitivity after Acute Exercise in Spontaneously Hypertensive Rats

“…In support of this, it has been shown that resting SNA and gain of baroreflex SNA control are reduced after prolonged elevations of arterial pressure (32). Consistent with the results of previous studies (10,11,32,33), in the present study SBP-LFamp, a marker of SNA (18), decreased in association with a reduction of arterial pressure after exercise as well as Iso+Phe infusion. On the other hand, BRS, which is predominantly determined by augmentation in cardiac vagal activity, increased after exercise but not after cessation of Iso+Phe infusion.…”

“…Apart from these chronic effects of exercise, a single bout of dynamic exercise is known to induce hypotension in the post-exercise period in hypertensive subjects (3) and spontaneously hypertensive rats (SHR) (4)(5)(6). Post-exercise hypotension (PEH) is associated with no change or a reduction of heart rate (HR) (7,8) and a reduction in cardiac (9) and peripheral sympathetic nerve activity (10,11). The reduction in blood pressure without a baroreflex-mediated compensatory tachycardia or sympa-thetic excitation suggests that a single bout of dynamic exercise resets the operating point of the arterial baroreflex to a lower pressure (5).…”

Kallikrein kinin system activation in post-exercise hypotension in water running of hypertensive volunteers

“…PEH appears to be a result of a persistent reduction in peripheral vascular resistance and due to the action of vasodilators [31][32][33][34][35][36][37][38]. Halliwill's group [31,[39][40][41] demonstrated that nitric oxide (NO), prostaglandins and histamine contributes to PEH.…”

Enhanced baroreflex sensitivity in free-moving calponin knockout mice

“…For example, the baroreflex sensitivity was reported to decrease during exercise (3, 4) and after exercise (5) compared with that before exercise. Recently, Kajeker et al (10) studied the role of rostral ventrolateral medulla neurons in controlling arterial baroreflex sensitivity and reported that GABA signaling in the brain stem increased after a bout of exercise to decrease arterial baroreflex sensitivity, leading to hypotension. Moreover, microinjection of the NO synthetase inhibitor into this area increased and the NO donor SNP reduced sympathetic outflow, perhaps via an inhibitory effect on sympathoexcitatory neurons in the brain stem (28).…”