Role of myocardial hypertrophy in trophic stimulation of indices of sympathetic cardiac innervation.
Indices of cardiac sympathetic innervation have commonly been found depressed in the failing, hypertrophied heart. In contrast, we have recently demonstrated that hemodynamically compensated, very gradually developing right ventricular hypertrophy is associated with an increase in sympathetic nervous markers. The present experiments were performed to corroborate these findings in a model of acutely induced right ventricular hypertrophy, and to further characterize changes in markers of autonomic innervation associated with cardiac hypertrophy. Male guinea pigs underwent either pulmonary artery banding (P) with an acutely constricting ligature, or bilateral stellate ganglionectomy (S), or both (PS). Appropriate sham procedures were performed in animals subjected to only one intervention; controls (C) underwent sham-S and sham-P. Groups of animals were sacrificed at 10 and 20 days after surgery. Cardiac tissues were weighed and subsequently analyzed for activities of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), two enzymes catalyzing the biosynthesis of catecholamines (CAs), and of choline acetyltransferase (CAT), a marker of parasympathetic activity, as well as for norepinephrine (NE). S resulted in profound depletions of cardiac NE of 88-92% and in significant decreases in the activities of DBH and TH. Marked right ventricular hypertrophy developed rapidly following P, and was not modified by S. Similar to our previous results, acute right ventricular hypertrophy was associated with moderate increases (10-20%) of sympathetic markers; following S, these increases (of presumably residual sympathetic innervation) were greatly enhanced, amounting to 171% and 105% for NE at 10 and 20 days, respectively. In contrast, sympathetic markers in the left ventricle of stellatectomized animals were not affected by P. Activity of CAT remained unaltered by the experimental interventions. Our experiments indicate that increases in markers of sympathetic innervation may be a common feature of the early, compensated stage of cardiac hypertrophy, regardless of its time course. Sympathetic neural mechanisms do not appear to play a stimulatory or trophic role in the hypertrophic process. Conversely, they seem to be secondary in nature, suggesting a possible stimulatory influence of hypertrophying myocardium on sympathetic cardiac nerves.
Lindpaintner
K
K
V.A. Medical Center, Cardiovascular Center, Iowa City, Iowa 52240.
Lund
D D
DD
Schmid
P G
PG
D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000033:anatomy & histology / Q000294:innervation*; D008297:Male; D009206:Myocardium / Q000032:analysis / Q000378:metabolism; D009638:Norepinephrine / Q000032:analysis; D010275:Parasympathetic Nervous System / Q000378:metabolism; D013233:Stellate Ganglion / Q000601:surgery; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000378:metabolism* / Q000601:surgery; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D002795:Choline O-Acetyltransferase; D009638:Norepinephrine