Effects of alpha2-adrenoceptor antagonists on metabolic processes of swine: I. Effects on nonesterified fatty acid and plasma urea nitrogen concentrations in jugularly catheterized pigs.

Abstract

The presence of alpha2-adrenoceptors in membranes from omental and s.c. adipose tissue from gilts and barrows was shown in saturation binding assays with [3H]yohimbine. Four trials tested effects of alpha2-adrenoceptor antagonists (A2AA) on plasma concentrations of NEFA and urea nitrogen (PUN). In Trial 1, barrows were given i.v. injections of saline, 200 microg/kg BW of one of three A2AA (efaroxan, idazoxan, or RX821002), or 25 microg/kg BW of isoproterenol. Concentrations of NEFA were measured in plasma harvested every 15 min from 1 h before to 2 h after treatment. Compared with results for saline-treated pigs, areas under the curve (AUC) for NEFA were increased (P < .05) by efaroxan, RX821002, and isoproterenol. In Trial 2, barrows received i.v. doses of saline, efaroxan (200 or 400 microg/kg BW), or RX821002 (200 or 400 microg/kg BW). Levels of NEFA were quantified in plasma obtained at 15-min intervals through 2 h after treatment. Among pigs treated with RX821002 at 400 microg/kg BW, mean NEFA AUC was more than three times greater (P < .05) than that for saline-treated animals. Trial 3 tested whether NEFA responses to A2AA were due to direct effects on alpha2-receptors or involved beta-adrenoceptor mediation. Pigs were first treated i.v. with saline or propranolol (1 mg/kg BW). One hour later, pigs were treated i.v. with RX821002 (400 microg/kg BW) or the beta-adrenoceptor agonist cimaterol (25 microg/kg BW). Compared to values for pigs treated with saline at both injections, NEFA AUC among pigs treated with saline at the first injection and RX821002 at the second doubled (P > .05). Plasma NEFA AUC among pigs treated with saline then cimaterol rose nearly fourfold (P < .05) compared with saline-treated controls. Mean NEFA AUC among propranolol-treated pigs was similar to values for saline-treated pigs, suggesting beta-adrenoceptor involvement in the effect of A2AA on NEFA. In Trial 4, pigs were treated s.c. 10 times at 8-h intervals with saline, RX821002 (400 microg/[kg BW x injection]), cimaterol (20 microg/[kg BW x injection]) or recombinant porcine somatotropin (rpST; 1 mg/[pig-injection]). After the 10th treatment, only cimaterol increased NEFA AUC compared to saline-treated controls (P < .05). Mean PUN AUC was reduced by RX821002 and rpST compared to controls; PUN among rpST-treated pigs was lower than that among RX821002-treated pigs (P < .05). In summary, A2AA increase lipolysis in swine by potentiating lipolytic effects of endogenous catecholamines on beta-adrenoceptors. Reduced PUN suggests improved nitrogen efficiency may result from treatment with A2AA.