Ventricular hypertrophy and presynaptic regulation of sympathetic function.
In normal heart, presynaptic cholinergic muscarinic and alpha 2-adrenergic mechanisms contribute to regional variations in the rate constant of norepinephrine turnover (kNE), an index of sympathetic neural function. To evaluate these mechanisms in the hypertrophied heart, pulmonary artery-constricted and sham-operated guinea pigs were pretreated with 1) saline vehicle (control) or 2) a combination of quinuclidinyl benzilate (Q), a muscarinic cholinergic antagonist, and yohimbine (Y), an alpha 2-adrenergic antagonist. An increase in kNE was determined in multiple regions of heart from incorporation of radiolabeled tyrosine into norepinephrine during a control period at 24 degrees C and again at 4 degrees C. In sham animals, kNE during cold stress was increased significantly (P less than 0.05) by Q + Y compared with vehicle, confirming that muscarinic cholinergic and/or alpha 2-adrenergic receptors exert a negative-feedback influence on sympathetic neurotransmitter synthesis. In pulmonary artery-constricted animals, in contrast, there were smaller increases in cardiac kNE compared with sham guinea pigs given Q + Y and subjected to cold stress. These data support the concept that muscarinic cholinergic and/or alpha 2-adrenergic presynaptic regulation of cardiac sympathetic function is altered in the hearts and vasculature of pulmonary artery-constricted guinea pigs.
Schmid
P G
PG
Veterans Affairs Medical Center, Cardiovascular Center, Iowa City, Iowa.
Whiteis
C A
CA
Lund
D D
DD
D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000503:physiopathology*; D003080:Cold Temperature; D003250:Constriction; D006168:Guinea Pigs; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011651:Pulmonary Artery; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*; D013696:Temperature; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D011813:Quinuclidinyl Benzilate; D009638:Norepinephrine