The influence of dihydroergotamine on adenosine-induced and reactive vasodilation after long and short periods of coronary artery occlusion was investigated in thoracotomized dogs. Adenosine-induced vasodilation (intracoronary administration) and vasodilation after long periods of coronary artery occlusion (25-35 beats) were similarly influenced, i.e. decreased by the i.v. administration of 10 mug/kg dihydroergotamine. By contrast vasodilation after short periods of coronary artery occlusion (4-7 beats) tended to be increased. This difference in response is thought to arise from two distinct mechanisms of coronary vasodilation after coronary artery occlusion depending on the duration of the occlusion period. The vasodilation after short periods of coronary artery occlusion possibly corresponds to physiological autoregulation. With longer periods of coronary artery occlusion an additional, consecutive mechanism is called into action.

Adenosine↗

PubMedDate not supplied

The effect of repeated intravenous and oral doses of molsidomine (N-carboxy-3-morpholino-sydnonimine-ethylester) on plasma renin activity and plasma catecholamine levels in conscious dogs.

The responses of plasma renin activity (PRA) and plasma catecholamine levels to molsidomine, administered both intravenously and orally, were investigated in conscious trained dogs. Intravenous administration of molsidomine at increasing dosage up to 0.4 mg/kg with a constant dose interval of 4 hours did not lead to a sustained increase in PRA. By contrast, a significant increase in PRA was still present after 4 hours on administration of 0.4 mg/kg molsidomine by the oral route. This longer-lasting increase in PRA following oral administration is discussed in relation to the conversion of molsidomine to an active metabolite in the liver. A reduction of dose interval to 3 hours or less led to a marked cumulative increase in PRA. It appears that substances acting via venous pooling lead to persistent activation of the renin angiotensin aldosterone system (RAA system), which counteracts its primary therapeutic effect. A slight increase in plasma noradrenaline levels was observed in response to repeated oral administration of 0.4 mg/kg molsidomine at a dose interval of 2 hours, indicating participation of the sympathetic nervous system in the counterregulatory process.

Animals↗

PubMedDate not supplied

The effect of a long-acting adenosine analog on blood flow through various organs in the dog.

Radioactively labeled microspheres were used to investigate the effect of 2',3'-di-O-nitro-5'-(N-ethylcarboxamido)-adenosine (10 micrograms/kg orally), a long-acting adenosine analog, on blood flow through various organs over an experimental period of three hours in conscious dogs. There was a significant increase in myocardial, cerebral, intestinal, and renal cortical blood flow, whereas the flow through skeletal muscle, liver, pancreas, and renal medulla was unaffected. The endocardial/epicardial flow ratio, which was more than one under control conditions, decreased significantly. Arterial blood pressure and heart rate remained virtually unchanged. Since the adenosine analog is rapidly and completely denitrated in vivo, the denitration product 5'-(N-ethylcarboxamide)-adenosine, a highly potent adenosine receptor agonist, must be considered as the vasoactive metabolite.

Adenosine↗