Abstract
Sympathetic hyperactivity and parasympathetic insufficiency characterize blood pressure (BP) control in genetic hypertension. This shift is difficult 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 normotensive (WKY) and spontaneously hypertensive rats (SHR), we injected intravenously 4-aminopyridine (4-AP), a voltage-sensitive K+ channel (KV) inhibitor. A femoral artery catheter monitored BP, an ascending aorta flow-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 in WKY, 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 (α2-adrenoceptor antagonist) prevented the TPVR down-regulation in WKY. Reserpine and prazosin (α1-adrenoceptor antagonist) eliminated the late vasoconstriction in SHR. Plasma epinephrine overflow increased in nadolol-treated SHR. Through inhibition of KV, 4-AP activated parasympathetic ganglion transmission and peripheral, neuronal norepinephrine release. The sympathetic component dominated the 4-AP–HR-response in SHR. α2-adrenoceptor-dependent vasodilatation opposed norepinephrine-induced α1-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. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.