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Biomedical subjects

R S Reneman

Publications and source records attributed to R S Reneman.

At least 325 records · Page 18Linked to original sources

Influence of guanethidine on the nicotinic effects of acetylcholine in atropinized dogs.

The influence of guanethidine on the nicotinic effects of acetylcholine was studied in anaesthetized atropinized dogs. Guanethidine (5 mg/kg i.v.) reversed the initial nicotinic pressor reaction, abolished the accompanying femoral vasoconstriction and reduced the increase of mean aortic flow. Therefore, nicotinic hypotension after guanethidine was due to a decrease of the peripheral vascular resistance. The height of the second pressor reaction was hardly affected by guanethidine. This drug inhibited the increases in mean aortic flow and heart rate but not the elevation of peripheral resistance, occurring at the secone nicotinic pressor phase. The present findings support the assumption that the initial hypertension is due to increased sympathetic outflow towards heart and vessels, whereas the second hypertension is due to adrenal medullary stimulation. The neurogenic femoral vasodilation at the onset of the second nicotinic pressor phase was blocked by guanethidine, which also inhibited the catecholamine-induced neurogenic vasodilation. These antagonisms may result from the interference of guanethidine with noradrenaline re-uptake.

Acetylcholine↗

Unusual mechanism of hypotensive activity exerted by erytrho-1-(1-[2-(1,4-benzodioxan-2-yl)-2-OH-ET-a1-4-piperidyl)-2-benzimidazolinone (R 28935).

In the dog, erythro-1-[2-(1,4benzodioxan-2-yl)-2-OH-ET]-4-piperidyl)-2-benzimidazolinone (R 28935) lowers the blood pressure for several hours at dosages of 80 mug/kg when injected intravenously, of 10 mug/kg when injected into the vertebral artery and of 1.25 mug/kg when injected suboccipitally. No alpha- or beta-receptor blocking activity can be elicited at these doses. The carotid occlusion reflex is markedly reduced by low doses of R 28935 (40 to 80 mug/kg i.v.), whereas the pressor response elicited by electrical stimulation of the hypothalamus remains unimpaired. The hypotensive effect of R 28935 is not antagonized by piperoxan, desmethylimipramine or nalorphine. This lowering of the blood pressure is associated with a decrease of the peripheral vascular resistance and with a slight tendency towards bradycardia. It is concluded that R 28935 is a potent blood pressure lowering drug, acting on the brain stem, presumably in the pontomedullary region--although the drug has no alpha-sympathomimetic activity.

Animals↗

An improved animal model for studying the effect of drugs on myocardial metabolism during ischemia.

An improved dog model to study the effect of drugs on myocardial metabolism during ischemia is described. A reproducible degree of ischemia could be obtained by partial occlusion of the anterior descending branch of the left coronary artery (LAD), using an inflatable cuff with a micrometer. The possibility of inducing the stenosis twice in the same animal has the advantage that the animal can be used as its own control. The reproducibility of the degree of ischemia was demonstrated by the nonsignificant differences in local venous lactate, inorganic phosphate, and glucose concentrations after the first and second stenosis. The mean pressure difference over the stenosis was used to express the degree of coronary artery narrowing. In this model, one does not have to rely on the collateral circulation in collecting local venous blood. Moreover, it is very likely that this blood is obtained from the most pronounced ischemic area, which was localized with radioactive microspheres. At this degree of stenosis, left ventricular function was not affected too much, as was demonstrated by the slight changes in dP/dt max, and systolic and diastolic aortic pressure after induction of the stenosis. The usefulness of our model to evaluate the activity of drugs is demonstrated by the effect of fentanyl, a potent morphine-like analgesic, on the poststenotic local venous lactate and inorganic phosphate concentrations.

Animals↗

Proceedings: The effects of hypothalamic and reflexogenic hypertension on renal and femoral circulation.

In anaesthetized dogs, electrical stimulation of the median posterior hypothalamus provoked hypertension accompanied by a decrease of renal blood flow and an increase of femoral blood flow. Similar hypothalamic reactions occurred after bilateral cervical vagotomy or after atropine, 2 mg/kg i.v. During reflexogenic hypertension induced by bilateral carotid occlusion in bivagotomized dogs, the renal and femoral blood flows were not significantly modified. The decrease of the renal blood flow and the increase of the femoral blood flow, during hypothalamic stimulation were greatly reduced or reversed after R 28935 equals erythro-1-(1--e12-(1,4-benzodioxan-2-yl)-2-OH-Et]-4-piperidyl)-2-benzimidaxolinone, 80 mug/kg i.v., but not after clonidine, 5 mug/kg i.v.

Animals↗