Prevention of exercise-induced cardiac hypertrophy in rats by chemical sympathectomy (guanethidine treatment).
The effect of 'chemical sympathectomy', produced by daily intraperitoneal injections of guanethidine sulphate for six weeks, was studied in sedentary rats and in rats chronically exercised by swimming. The guanethidine-treatment itself caused the following changes. There was a reduction in the rate of weight gain resulting in a 7% lower final body weight. Organ content of noradrenaline was decreased by 90% in spleen and submandibular glands and by 83% in the heart. Urinary excretion of noradrenaline was also decreased, but to a lesser degree, both during rest (45% lower) and after acute exercise (46% lower), while the urinary excretion of adrenaline was no different from that of controls. There was a compensatory adrenal hypertrophy in the guanethidine-treated rats, with a significant increase in adrenal catecholamine levels that was more pronounced for noradrenaline (+45%) than for adrenaline (+11%). Chronic physical exercise produced the expected degree of cardiac hypertrophy in untreated rats, but this adaptive cardiac hypertrophy was completely absent in the exercised guanethidine-treated rats. The results indicate, firstly that a good degree of chemical sympathectomy was obtained and that the persistence of a considerable urinary excretion of catecholamines in the guanethidine-treated rats was due to a compensatory increase in the secretory activity of the adrenal medulla. Secondly, it is suggested that the adaptive cardiac hypertrophy produced by chronic exercise is not caused by a direct effect of the increased work load on the cardiac muscle cell, but is instead mediated by release of a trophic factor from cardiac sympathetic nerves, probably noradrenaline itself but possibly a secretory protein.
Ostman-Smith
I
I
Department of Physiology I, Karolinska Institute, S-104 01 Stockholm, Sweden.
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000652:urine; D006145:Guanethidine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D006984:Hypertrophy / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013563:Sympathectomy, Chemical / Q000009:adverse effects*; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects / Q000378:metabolism*; D013565:Sympatholytics / Q000494:pharmacology
D002395:Catecholamines; D013565:Sympatholytics; D006145:Guanethidine