Depletion and recovery of catecholamines in several organs of rats treated with reserpine.

Chemical sympathectomy with reserpine depletes catecholamines in every neuronal or nonneuronal cell producing a nonspecific temporal sympathectomy. After reserpine administration, most of the drug is distributed to tissues based on their blood flow and would then either be metabolized or be reversibly bound in lipid depots from where it might be released. Consequently, reserpine concentration and the catecholamine-depleting effect in the various tissues are expected to differ according to the route of administration. This study was designed to compare the effects of intraperitoneal (i.p.) and subcutaneous (s.c.) administration of reserpine on catecholamine depletion and recovery in the liver, portal vein, and adrenal gland on days 1, 4, and 10 after reserpine dosage. Catecholamine determinations were extended to 25 days after the treatment only in s.c. reserpine-treated rats and adding samples of heart and brown adipose tissue to the testing. I.p. and s.c. reserpine administration had the same norepinephrine-depleting effect in the portal vein and liver but full recovery was present in both tissues only in i.p. reserpine-treated rats. In the adrenal gland, both routes of administration produced the same depleting and recovery effect of norepinephrine and epinephrine concentrations. A significant temporary overshoot in epinephrine levels was observed several days after s.c. reserpine treatment. Except for the liver, reserpine injected s.c. depleted norepinephrine concentrations significantly in all other tissues up to the end of the experiment. Our results suggest that chemical sympathectomy caused by reserpine administered s.c. produces a generalized and prolonged decrease in peripheral sympathetic activity that could be compensated by an increase in activity of the adrenal gland.

Epinephrine and dopamine colocalization with norepinephrine in various peripheral tissues: guanethidine effects.

Chemical sympathectomy with guanethidine (Gnt) selectively destroys the postganglionic noradrenergic neurons, whereas dopaminergic fibers and nonneural catecholamine-secreting cells are spared. As a result, the relative proportions of norepinephrine (NE), epinephrine (E), and dopamine (DA) in tissues can be differentially affected. This study was done to show the possible differences in the relative amount of catecholamines in some organs and tissues that might indicate the nature of the secretory cells from which they originate. The contents of NE, E, and DA were assessed in rats neonatally treated with Gnt. Gnt-treated rats showed significantly lower levels of NE (P < 0.01) in all tissues except the adrenal gland and paraganglia. Epinephrine was present in all tissues with mean levels below 25 ng/g, with the exception of the adrenal gland (700 microg/gland) and paraganglia (100 ng/g). Only the heart showed lower values in Gnt-treated rats. Mean DA levels were also very high in paraganglia (530 ng/g). In the Gnt-treated rats, DA levels fell practically to zero except in the duodenum, mesentery, and adrenal, whereas there were high levels in the paraganglia, which were significantly different from controls. The results suggest that the three catecholamines are contained mainly in noradrenergic sympathetic fibers of muscle, white adipose tissue, heart, liver, pancreas, and spleen. The duodenum and mesentery may have dopaminergic fibers or E- and DA-containing nonneural cells. Hepatic-vagus paraganglia contain all the catecholamines in relatively high amounts in nonneural cells, and Gnt treatment raises DA levels without affecting the other amines.

Chemical sympathectomy alters food intake and thermogenic responses to catecholamines in rats.

It has been suggested that the sympathetic nervous system contributes to the short-term control of feeding. The adrenergic innervation of some splanchnic organs seems to be especially involved in such processes, since catecholamines reduce feeding only when injected intraperitoneally or intraportally. In this work, the effects of neonatal sympathetic denervation with guanethidine (Gnt) upon food intake were assessed in adult rats. Gnt-treated male rats had lower body weight gain. The hypophagic response to intraperitoneal (ip) norepinephrine was 70% higher in Gnt-treated animals as compared to controls (P < 0.05); that of epinephrine (E) by 33% (P < 0.05) and that of isoproterenol was not significantly modified. As in normal rats, the hypophagic effect was much stronger after ip than after intramuscular (im) administration (P < 0.05). On the other hand, resting oxygen consumption (VO2) was consistently lower in denervated animals. Ip E administration did not modify VO2, while im E caused increased motor activity and VO2 (P < 0.05). In contrast to control rats, the respiratory exchange ratio in ad libitum fed Gnt rats did not decrease after Ip E administration, suggesting a lack of effect upon lipid mobilization. The lower rate of body weight gain induced by neonatal Gnt sympathectomy might be due to lower daily food intake possibly related, in part, to the sensitization of the alpha-adrenergic porto-hepatic response to endogenous catecholamines. Compared with controls, Gnt-treated rats also showed a limited thermogenic capacity not related to feeding, and a greater degree of carbohydrate oxidation, possibly due to a defect in E-induced lipolysis, which is beta-adrenergic.