Pharmacological comparison of isolated monkey and dog cerebral arteries.

Abstract

SUMMARY Pharmacological differences between canine and monkey basilar arteries were studied in vitro. The constrictor response of canine basilar artery to either norepinephrine or an a ( -adrenoceptor agonist phenylephrine was partly inhibited by an a 2 -adrenoceptor antagonist yohimbine but not by an a,-adrenoceptor antagonist prazosin. The contraction elicited by an » 2 -adrenoceptor agonist clonidine was inhibited by neither prazosin nor yohimbine. These results suggest that the receptors in canine basilar artery which mediate norepinephrine-induced contraction are different from classical a, or a 2 -adrenoceptors, although they more closely resemble the a 2 -rather than the a|-subtype. Using monkey basilar artery, phenylephrine produced the same amplitude of maximum contractile response as norepinephrine, though a much higher concentration of phenylephrine than norepinephrine was needed in order to elicit that maximum response. Clonidine did not elicit contractions. The contraction induced by norepinephrine was markedly suppressed by both prazosin and yohimbine in a noncompetitive fashion. The constrictor response of monkey basilar artery to norepinephrine, therefore, appears to be mediated by «,-like adrenoceptors. Comparison of ED50 values for thromboxane A2 revealed that the monkey basilar artery was more sensitive to thromboxane A2 than that of the canine. Prostaglandin F2a produced a larger maximum contraction in monkey basilar arteries than in canine basilar arteries, although the ED 50 values for monkey basilar arteries were larger than those for canine basilar arteries. The ED 50 values for serotonin in canine basilar arteries were a little less than those for monkey basilar arteries, although both arteries produced nearly identical maximum contractions.Stroke Vol 16, No 3, 1985 SPECIES DIFFERENCES in the constrictor responses of cerebral arteries to vasoactive agents are of contemporary interest with regard to the pathophysiology of the cerebral circulation. Hardebo, et al 1 reported that histamine was a strong vasoconstrictor in rabbit cerebral arteries but a prominent vasodilator in human cerebral arteries. Norepinephrine is reported to be a much more potent cerebral artery spasmogen in man than in experimental animals such as rats, rabbits or dogs, 1 2 and a potential vasodilator in pig cerebral arteries. 3Postjunctional a-adrenoceptors have recently been subclassified into a,-and a,-type adrenoceptors, based on relative potencies of selective agonists and antagonists.4 " 8 Experiments using such selective agonists and antagonists have suggested that the vasoconstrictor responses of feline middle cerebral artery 9 -l0 and canine basilar artery 2 " to exogenous norepinephrine are predominantly mediated by the a,-adrenoceptor subtype. However, the nature of a,-adrenoceptors in canine cerebral arteries still remains controversial since some discrepancy exists between the experimental results by Sakakibara et al" and those by Toda.2 Sakakibara et al" have reported that an a 2 -agonist clonidine el...

Ontogenic increase in PGE2 and PGF2α receptor density in brain microvessels of pigs

“…In the adult, PGE2 via EP, and PGF2. via FP receptors activate phospholipase C which results in IP3 formation (Heaslip & Sickels, 1989;Suba & Roth, 1990), leading to increases in intracellular calcium (Berridge & Irvine, 1989) and subsequent vasoconstriction; this vasoconstriction, which has been shown in cerebral vessels (White & Hagen, 1982;Hayashi et al, 1985;Sasaki et al, 1985;Chemtob et al, 1989), may significantly prevent CBF from increasing when systemic blood pressure rises (Rapela & Green, 1964). In contrast in the newborn, due to the relative deficiency in PGE2 and PGF2, receptors on the cerebral vasculature, an increase in PGE2 and PGF2¢ levels as blood pressure is raised from its basal value (Chemtob et al, 1990a) might not be able to produce sufficient vasoconstriction to prevent an increase in CBF (Chemtob et al, 1989).…”

“…Prostanoids exert their effects through specific receptors, defined as EP receptors for PGE2 and FP receptors for PGF2., (Kennedy et al, 1982;Sasaki et al, 1985;Coleman, 1987;Santoian et al, 1989;Abran et al, 1994). EP receptors are further classified into EP1, EP2 and EP3 subtypes (Coleman et al, 1987;Coleman, 1987;Halushka et al, 1989;Eglen & Whiting, 1989).…”

Development of anEx VivoModel for the Study of Cerebrovascular Function Utilizing Isolated Mouse Olfactory Artery

“…Tissue-organ bath systems have been widely used in ex vivo studies for cerebrovascular function by measuring the forces in strips or rings of isolated vessel segments 9 , 19 , 20 , 23 , 25) , whereas the transcranial window methods have been developed to study the vessel function in vivo in live experimental rodents 18) , in particular, in leptomeningeal arteries and arterioles (only to a depth of 250 µm from the cortical surface) 17 , 24) . The ex vivo studies would have several advantages over the in vivo cranial window methods in the following respects : 1) this method allows dose-escalating and/or antagonism studies, 2) biochemical degradation and/or metabolism of applied agents is negligible, 3) the effects of nonvascular cells (i.e., glial and neuronal cells) can be removed, and 4) studies can be performed under physiologic as well as pathophysiological conditions.…”

Heterogeneous vasomotor responses of anatomically distinct feline cerebral arteries

“…Other than differences based purely on the anatomical location of the artery, both neurotransmitter concentrations and the density of innervation may be a function of vessel calibre within the cerebrovascular bed; such is the case for 5-hydroxytryptamine (Edvinsson et al, 1983a;Scatton et al, 1985). Another characteristic of the cerebral arteries resides in the heterogeneity of the vascular responses to agonists and antagonists not only between species (Chiba & Tsuji, 1985;Hamel et al, 1985;Sasaki et al, 1985;Usui et al, 1985) but also between anatomically distinct vessels (Toda, 1976) and, further, between different segments of the same vessel in a given species (Toda et al, 1984).…”