Responses of isolated dog cerebral and peripheral arteries to prostaglandins after application of aspirin and polyphloretin phosphate.

Abstract

SUMMARY In helically cut strips of dog cerebral, coronary, mesenteric and femoral arteries, the contractile response to prostaglandin (PG) F 2( , and E 2 , relative to contractions induced by 30 mM K + , did not appreciably differ, whereas relaxations induced by PGE, relative to those induced by 10 * M papaverine were significantly different; the least in cerebral arteries and the greatest in mesenteric arteries. The relaxation of human cerebral arteries in response to PGE, was similar to that of dog cerebral arteries. Treatment for 60 min with polyphloretin phosphate (3 X 10" and 10 ' g/ml) suppressed the contractile response to PGF 2( , and E 2 but did not alter the response to 25 mM K + . The relaxing effect of PGE, was not influenced. Aspirin (5 X 10" and 2 X 10 ' M) significantly potentiated the contractile response to PGF to and E 2 but did not alter the relaxation induced by PGE,. In contrast, contractions induced by serotonin were attenuated. It is concluded that dog cerebral, coronary, mesenteric and femoral arteries relaxed differently in response to PGE,. It appears that arterial responses to vasoconstricting PCs, but not to the vasodilating PG, are significantly attenuated by polyphloretin phosphate and potentiated by aspirin.PROSTAGLANDINS (PGs) induce changes in systemic blood pressure, regional blood flow and tone of vascular smooth muscle. Alterations induced by a variety of PG derivatives differ markedly, and even the same PGs sometimes elicit opposite actions on vessels from various species. Different responses of cerebral vessels to PGEi and E 2 have been reported, 16 however, it is generally agreed that PGF 2a causes constriction in cerebral vessels.The ability of polyphloretin phosphate (PPP) to antagonize the effect of PGE 2 on intraocular pressure was first demonstrated by Beitch and Eakins.7 PPP does not antagonize all actions of PGs on uterine, tracheal and bronchial smooth muscles. "10 Aspirinlike anti-inflammatory agents inhibit the biosynthesis of PGs in isolated tissues and whole animals, 11 ' 12 but the interaction between PGs and aspirin or indomethacin, related to responses of vascular smooth muscles, has not been clarified.The present study was undertaken to compare the actions of PGE,, E 2 and F 2a on isolated dog cerebral arteries with their actions on coronary, mesenteric and femoral arteries and to analyze the antagonistic action of PPP in these arteries. Alterations in the response of the arteries to PGs after aspirin and indomethacin application were also investigated. MethodsMongrel dogs of both sexes, weighing 7 to 15 kg, were anesthetized with intraperitoneal injections of sodium pentobarbital in a dose of 50 mg/kg and sacrificed by bleeding from common carotid arteries. The brain and heart were rapidly removed. Basilar and middle cerebral arteries (0.5 to 0.8 mm outside diameter) and ventral interventricular branches of the left coronary artery (0.6 to 0.9 mm) were isolated. Distal portions of the mesenteric (0.5 to 0.8 mm) and femoral arteries (0.5 to 0.8 mm) were also...

Effects of subarachnoid haemorrhage on intracranial prostaglandins.

“…Brandt et aP3 have shown that there is considerable individual variability in the spectrum of reactivity of cerebral arteries from man in vitro to different stimuli such as high potassium, prostaglandins and biogenic amines (serotonin, noradrenaline). However, in both dog and man, in vitro contractions of cerebral arteries are produced with PGF2a and PGE2 of concentrations above 100 nmol/1.24 25 Lesser concentrations may produce just detectable responses, and may potentiate the effects of other vasoconstrictor agents at these low levels. The combined concentrations of the two cerebral vasoconstrictors PGF2aand PGE2 of around 2 nmol/l in cistemal CSF 3 days and 0-5 nmol/l 7 days after subarachnoid haemorrhage in the dog, and of around 3 nmol/l in lumbar CSF in man 7 days after subarachnoid haemorrhage, seem a little low for potent vasoconstrictor action.…”

Prejunctional Regulation by Endogenous and Exogenous Acetylcholine of Adrenergic Nerve Function in Isolated Canine Mesenteric Arteries.

“…Isometric mechanical responses were recorded on an ink-writing oscillograph. The resting tension was adjusted to 1.5 g, which is optimal for inducing maximum contraction (14). Norepinephrine (10-~ to 10-5 M) was applied cumulatively to the bathing media to obtain the concentration-response curve.…”

Potentiation by hypoxia of contractions caused by angiotensin II in dog and monkey cerebral arteries.

“…In the cerebral arterial strips, only PGI2 produces relaxation among the cyclooxygenase products used. [17][18][19] In the arteries treated with ON03708, the action of arachidonic acid was suppressed by hypoxia.…”