Effect of selective beta-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

There is evidence for participation of peripheral β-adrenoceptors in delayed liquid gastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At). The present study aimed to determine whether β-adrenoceptors are involved in delayed GE induced by phenylpyrazole derivatives and the role of the prevertebral sympathetic nervous system in this condition. Male Wistar rats weighing 220-280 g were used in the study. In the first experiment rats were intravenously pretreated with vehicle (V), atenolol 30 mg/kg (ATE, β1-adrenergic antagonist), or butoxamine 25 mg/kg (BUT, β2-adrenergic antagonist). In the second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA, β3-adrenergic antagonist). In the third experiment, rats were subjected to surgical resection of the celiac-superior mesenteric ganglion complex or to sham surgery. The groups were intravenously treated with saline (S), 240 µmol/kg Dp, AA, or At, 15 min after pretreatment with the antagonists or V and nine days after surgery. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR (means±SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dp vs V+Dp: 35.0%±5.1% vs 56.4%±2.7%) and At (BUT+At vs V+At: 33.5%±4.7% vs 52.9%±2.6%) on GE, and significantly reduced (P<0.05) the effect of AA (BUT+AA vs V+AA: 48.0%±5.0% vs 65.2%±3.8%). ATE, SRA, and sympathectomy did not modify the effects of treatments. These results suggest that β2-adrenoceptor activation occurred in delayed liquid gastric emptying induced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, and antipyrine. Additionally, the released neurotransmitter did not originate in the celiac-superior mesenteric ganglion complex.

Atenolol or butoxamine injection at the lateral septum doesn't inhibit male sexual behavior in rats.

To investigate the role of specific adrenoreceptors subtypes on sexual behavior, atenolol, butoxamine, a mixture of atenolol and butoxamine, and saline (vehicle) were injected into the lateral septum in four different groups of sexually active male rats. Application of a mixture of atenolol and butoxamine produced inhibition of copulatory activity. On the other hand, application of either atenolol or butoxamine alone did not inhibit copulatory activity. But it produced stimulation of some of the components of male sexual behavior. Inability of either atenolol or butoxamine to inhibit the male sexual behavior, and inhibition of the same by the mixture of atenolol and butoxamine, indicate that both beta-adrenoreceptors at the lateral septum are involved in the elaboration of male sexual behavior. Stimulation of some components of sexual behavior on application of atenolol or butoxamine could be attributed to an unbalanced activity of beta-adrenoreceptors.

Hypotensive effect of intracerebroventricular injection of norepinephrine and its modulation by alpha and beta adrenergic blockers in conscious rabbits.

The present study was designed to investigate the role of central adrenoceptors in the hypotensive effect of intracerebroventricular (ICV) injection of norepinephrine (NE) in conscious rabbits. Experiments were carried out on 19 adult rabbits (oryctolagus cuniculus) of either sex. A dose-dependent hypotensive response to ICV injection of NE was observed with no significant change in heart rate. The hypotensive response of NE was blocked 74.2 +/- 0.7% by yohimbine (alpha-2 adrenergic blocker), and 25.0 +/- 0.5% by metoprolol (beta-1 adrenergic blocker). NE response was not affected either by prazosin or butoxamine (alpha-1 and beta-2 adrenergic blockers respectively). The results suggest that the dose-dependent hypotensive response of ICV administered NE is mediated through alpha-2 and beta-1 central adrenoceptors.

The effect of beta-adrenoceptor antagonists alone and in combination with a GABA-elevating agent on isoniazid-induced convulsions in rats.

A delay in the onset of isoniazid-induced convulsions was found in rats pretreated with the beta 2-adrenoceptor blocker, butoxamine and the nonspecific beta-blocker, propranolol. In these animals the convulsive responses were inhibited in a dose dependent manner. These compounds were found to be effective even after the induction of convulsions. The beta 1-blocker, acebutolol was able to protect rats only when injected prior to the challenge. The anticonvulsant effect of acebutolol and propranolol but not that of butoxamine was found to be enhanced in animals pretreated with a gamma-aminobutyric acid (GABA) elevating agent, aminooxyacetic acid (AOAA). The findings indicate that the GABA-mediated anticonvulsant action of AOAA seems to be additive with that resulting from beta 1 but not beta 2-blockade.

Functional ß2-adrenoceptors in right atria isolated from footshock-stressed rats

The participation of ß2-adrenoceptors in the chronotropic response was evaluated in righ atria isolated from rats submitted to daily footshock stress for three days. Footshock increased both the sensitivity to salbutamol and the pA2 of butoxamine. These results provide additional support for the proposal that repeated footshock stress increases the functional of rat atrial postjunctional ß2-adrenoceptors

Experimental Study of Practolol on Cardiac Arrhythmias

Recently several adrenergic beta receptor blocking agents such as dichloroisoprenaline, pronethalol, INPEA, H13/57, propranolol, sotalol, tolamolol, practolol and butoxamine were reported. It has been postulated for some time that there are two subgroups of beta receptors: cardiac receptors (beta 1-eceptor) and peripheral receptors (beta 2-receptor) responsible for vasodilatation and broncholdilatation. More recently, the cardioselective beta blockers have been developed; for example, practolol, and talamolol. Rabbits were anesthetized by the peritoneal injection of urethane 1 gm/kg and observed for 30 minutes. Arrhythmias were produced with lanatocide-C and norepinephrine through the ear vein of the anesthetized rabbits. Arrhythmias such as premature ventricular contraction and ventricular tachycardia were present within 7 minutes to 20 minutes after the injection of lanatocide-C 0.9mg, and within 15 seconds to 2 minutes after the injection of norepinephrine 150ug. Propranolol or practolol were injected before and after the production of the arrhythmias and so Lead II of the electrocardiogram was obtained from nedle electrodes inserted into the skin. Practolol was compared with propranolol on the changes of the heart rates and the arrhytmias produced by the injection of norepinephrine and lanatocide-C. The intravenous injection of propranolol and practolol reduced the heart rate but practolol reduced much lesser than propranolol. All of arrhythmias produced by lanatocide-C in anesthetzedrabbits were not abolished by practolol, but it blocked and prevented the development of arrhythmias in anesthetized rabbits on the administration of norepinephrine.