Dual effects of norepinephrine and mechanisms of baroreceptor stimulation.
The aim of this study was to determine the mechanism of action of norepinephrine (NE) on arterial baroreceptors (BRs), with the focus on regularly discharging, presumably myelinated fibers. With the use of an in vitro aortic arch/aortic nerve preparation from rats, BR single-fiber discharge was recorded simultaneously with aortic pressure and diameter. At constant suprathreshold pressure, NE had two dose-dependent effects. Inhibition was produced at low concentrations (10(-10)-10(-7) M), whereas excitation was produced at high concentrations (10(-6)-10(-5) M). Inhibition was attributed to BR unloading since the response was consistent with the fall in diameter, was mimicked by angiotensin II (10(-10)-10(-6) M), and was prevented by pretreatment with the smooth muscle relaxant sodium nitroprusside (10(-6) M) or the selective alpha 1-adrenergic antagonist, prazosin (10(-6) M). Excitation was attributed to direct activation of the BR endings since this response was independent of changes in diameter, was not mimicked by angiotensin II, and was not prevented by sodium nitroprusside but was blocked by prazosin. These results indicate that NE has two modes of action, one mediated by contraction of local vascular smooth muscle and the other due to direct excitation of the nerve endings. It was also found that BR discharge at given diameters decreased more when pressure was lowered (smooth muscle passive) than when the aorta constricted (smooth muscle active). Furthermore, if diameter was held constant during smooth muscle contraction, discharge increased, as opposed to decreasing at constant pressure. These later results suggest that BR responses to vasoactive agents reflect not only changes in wall dimension but perhaps changes in wall tension and/or the coupling relation between BR and smooth muscle structures.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D001696:Biomechanical Phenomena; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011921:Rats, Inbred WKY; D013268:Stimulation, Chemical; D013565:Sympatholytics / Q000494:pharmacology
D013565:Sympatholytics; D000804:Angiotensin II; D009638:Norepinephrine