Mechanisms of denervation supersensitivity in regionally denervated canine hearts.
Mechanisms responsible for "denervation supersensitivity" in regionally denervated canine hearts were examined by measuring beta-adrenergic receptor density and affinity and the density of the alpha-subunit of the stimulatory G protein (Gs alpha). Sympathetic denervation was produced by applying an epicardial strip of phenol midway between the left ventricular (LV) base and apex. Six to eight days after denervation, dogs were anesthetized and then underwent functional studies (n = 4) or hearts were excised for biochemical analyses (n = 6). Biochemical studies were also done on 3 nondenervated hearts. Effective refractory periods (ERPs) were measured in innervated (base) and denervated (apex) LV myocardium. During sympathetic stimulation (2 and 4 Hz), the ERP shortened more (P < 0.05) at basal than at apical sites, whereas during norepinephrine infusion (0.05 to 0.5 mg.kg-1 x min-1), the ERP shortened more (P < 0.001) at apical than at basal sites. In regionally denervated hearts, however, the density and affinity of beta-adrenergic receptors did not differ significantly (P > 0.2) in nondenervated basal compared with denervated apical myocardium. Quantitative immunoblotting of the Gs alpha demonstrated that the density of the 47- and 52-kDa subunits was also similar (P > 0.6) in basal compared with apical myocardium from regionally denervated hearts. In addition, beta-adrenergic receptor density and affinity and Gs alpha density did not differ significantly (P > 0.5) in basal compared with apical myocardium from nondenervated control hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
Warner
M R
MR
Department of Pharmacology, Indiana University School of Medicine, Krannert Institute of Cardiology, Indianapolis 46202.
Wisler
P L
PL
Hodges
T D
TD
Watanabe
A M
AM
Zipes
D P
DP
D000818:Animals; D003714:Denervation; D004285:Dogs; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D015151:Immunoblotting; D009638:Norepinephrine / Q000494:pharmacology; D019800:Phenol; D010636:Phenols / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology
D010636:Phenols; D011943:Receptors, Adrenergic, beta; D019800:Phenol; D009638:Norepinephrine