Sympathetic hyperactivity and parasympathetic insufciency characterize blood pressure (BP) control in genetic hypertension. This shift is difcult to investigate in anesthetized rats. Here we present a pharmacological approach to simultaneously provoke sympathetic and parasympathetic transmitter release, and identify their respective roles in the concomitant cardiovascular response. To stimulate transmitter release in anesthetized nor-motensive (WKY) and spontaneously hypertensive rats (SHR), we injected intravenously 4-aminopyridine (4-AP), a voltage-sensitive K + channel (K V) inhibitor. A femoral artery catheter monitored BP, an ascending aorta ow-probe recorded cardiac output and heart rate (HR). Total peripheral vascular resistance (TPVR) was calculated. 4-AP-induced an immediate, atropine (muscarinic antagonist)- and hexamethonium(ganglion blocker)-sensitive bradycardia inWKY, and in both strains, a subsequent, sustained tachycardia, and norepinephrine but not epinephrine release. Reserpine (sympatholytic), nadolol (β-adrenoceptor antagonist) or right vagal nerve stimulation eliminated the late tachycardia, adrenalectomy, scopolamine (central muscarinic antagonist) or hexamethonium did not. 4-AP increased TPVR, transiently in WKY but sustained in SHR. Yohimbine (α 2-adrenoceptor antagonist) prevented the TPVR down-regulation in WKY. Reserpine and prazosin (α 1-adrenoceptor antagonist) eliminated the late vasoconstriction in SHR. Plasma epinephrine overow increased in nadolol-treated SHR. Through inhibition of K V, 4-AP activated parasympathetic ganglion transmission and peripheral, neuronal norepinephrine release. The sympathetic component dominated the 4-AP-HR-response in SHR. α 2-adrenoceptor-dependent vasodilatation opposed norepinephrine-induced α 1-adrenergic vasoconstriction in WKY, but not SHR. A βAR-activated, probably vagal afferent mechanism, hampered epinephrine secretion in SHR. Thus, 4-AP activated the autonomic system and exposed mechanisms relevant to hypertensive disease. © 2011 Berg and Jensen.
Berg, T., & Jensen, J. (2011). Simultaneous parasympathetic and sympathetic activation reveals altered autonomic control of heart rate, vascular tension, and epinephrine release in anesthetized hypertensive rats. Frontiers in Neurology, NOV. https://doi.org/10.3389/fneur.2011.00071