Sequential Modulation of Cardiac Autonomic Control Induced by Cardiopulmonary and Arterial Baroreflex Mechanisms

Background—Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate.Methods and Results—Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to −40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (αLF) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at −10, R-R interval at −20, SAP at −40, and the indexes αLFand baroreceptor sensitivity at −30 and −20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at −20 mm Hg. The normalized low-frequency component of R-R variability (LFR-R) progressively increased and was significantly higher than in the control condition at −15 mm Hg.Conclusions—Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LFR-R, which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control

The role of beta-endorphin in central cardiovascular control /

The role of $beta$-endorphin in the cardiovascular depressor response elicited by clonidine or by electrical stimulation of the nucleus tractus solitarii (NTS) was studied in awake as well as anesthetized rats. The opiate antagonists, naloxone or naltrexone, inhibited the hypotensive and bradycardic effects of clinidine in spontaneously hypertensive rats (SHR), in normotensive and steroid-salt hypertensive Sprague-Dawley (S-D) rats, but not in normotensive Wistar Kyoto (WKY) rats. The brain ACTH/$beta$-endorphin fibre system originating in the arcuate nucleus was eliminated by neonatal treatment with monosodium glutamate (MSG). MSG-treatment abolished the naloxone-sensitive component of the effects of clonidine in SHR, while the naloxone-resistant effects of clonidine in WKY were not affected. Intra-NTS microinjection of clonidine (5 nmol) decreased blood pressure and heart rate, and these effects were inhibited by previous intra-NTS injection of dl- but not d-naloxone (270 pmol) in both SHR and normotensive S-D rats. Intra-NTS injection of $beta$-endorphin (0.3 pmol) also reduced blood pressure and heart rate in both rat strains. In SHR, the effects of both clonidine and $beta$-endorphin were inhibited by ICI 174864, a selective $delta$ receptor antagonist, but not by $beta$-funaltrexamine, a selective $mu$ receptor antagonist (270 pmol, intra-NTS). In contrast, in normotensive S-D rats only the $mu$ and not the $delta$ antagonist was an effective inhibitor. In S-D rats made hypertensive by prolonged treatment with a mineralocorticoid and salt, the pattern of inhibition was the same as in SHR. The depressor baroreflex response was elicited by electrical stimulation of the NTS. In SHR, intra-NTS injection of an antiserum to $beta$-endorphin inhibited, while an antiserum to met-enkephalin potentiated the hypotensive and bradycardic response to NTS stimulation. In similar experiments in WKY rats, the antisera were ineffective.These findings are interpreted to indicate that the cardiovascular effects of clonidine involve release of $beta$-endorphin and subsequent stimulation of opiate receptors in the NTS. The most likely source of $beta$-endorphin is nerve terminals whose cell bodies are in the arcuate nucleus. The released $beta$-endorphin acts on $mu$ receptors in normotensive or $delta$ receptors in hypertensive rats, with no evidence for the additional involvement of peripheral opiate receptors. (Abstract shortened with permission of author.