Aortic barodenervation up-regulates alpha2-adrenoceptors in the nucleus tractus solitarius and rostral ventrolateral medulla: an autoradiographic study.
Earlier findings have shown that alpha2-adrenoceptors in the nucleus tractus solitarius and rostral ventrolateral medulla modulate baroreflexes. The present study investigated whether attenuation of baroreflexes induced by surgical interruption of aortic baroafferents is related to an alteration of alpha2-adrenoceptor binding in these regions of the brainstem. In vitro autoradiography was utilized to assess the density and binding dissociation constant (affinity) of alpha2-adrenoceptors in the rostral ventrolateral medulla and in the middle and rostral portions of the nucleus tractus solitarius of aortic-barodenervated and sham-operated rats. Compared to sham operation, aortic barodenervation caused an acute rise in mean arterial pressure and heart rate and a significant reduction in baroreflex sensitivity. Two days later, mean arterial pressure and heart rate of conscious aortic-barodenervated rats subsided to sham-operated levels, whereas the baroreflex sensitivity remained significantly (P<0.05) reduced when measured by phenylephrine (0.55+/-0.08 vs 1.26+/-0.07 ms/mmHg) or nitroprusside (0.43+/-0.06 vs 1.01+/-0.09ms/mmHg). Examination of brainstem coronal sections obtained from separate groups of rats 48 h after surgery and preincubated with [3H]rauwolscine (0.5-16 nM) revealed that labeling of alpha2 binding sites was saturable and of high affinity. Scatchard analysis of the saturation isotherms obtained from the three brain areas of sham-operated rats showed an uneven distribution of alpha2 binding sites; the rostral nucleus tractus solitarius exhibited the highest density and lowest affinity. Aortic barodenervation caused region-dependent changes in the binding activity of alpha2-adrenoceptors. These changes comprised significant (P<0.05) increases in the density of alpha2-adrenoceptors in the middle nucleus tractus solitarius (436+/-60 vs 240+/-50 fmol/mg protein) and rostral ventrolateral medulla (350+/-67 vs 194+/-35 fmol/mg protein) compared with sham-operated rats; no significant changes occurred in the rostral nucleus tractus solitarius. The affinity of alpha2 binding sites was not changed by aortic barodenervation in any of the three brain regions. These findings suggest that attenuation of baroreflexes produced by aortic barodenervation coincides with up-regulation of alpha2-adrenoceptors in brainstem areas that play critical roles in the control of cardiovascular functions.
El-Mas
M M
MM
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, U.S.A.
Abdel-Rahman
A A
AA
D000818:Animals; D001011:Aorta / Q000502:physiology*; D001345:Autoradiography; D001794:Blood Pressure / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D017552:Solitary Nucleus / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
D018341:Receptors, Adrenergic, alpha-2; D009599:Nitroprusside; D010656:Phenylephrine