Mechanism of CO2 response in cerebral arteries of the newborn pig: role of phospholipase, cyclooxygenase, and lipoxygenase pathways.

Abstract

The role of phospholipase, lipoxygenase, and cyclooxygenase pathways in the mechanism of the cerebrovascular response to CO2 and H+ was investigated in newborn piglets. Responsiveness of pial arterioles, 48-206 micron diameter, to inhalation of 6% CO2 and to suffusion of acidic cerebrospinal fluid (CSF, pH = 6.84), adenosine (10(-4) M), or theophylline (10(-2) M) was studied using a closed cranial window. Pial arteriolar diameter was measured using intravital microscopy. Phospholipase inhibitors quinacrine hydrochloride (10(-4) M in CSF) and p-bromophenacyl bromide (10(-4) M in CSF) abolished the CO2 vasodilation from delta diameter = 27 +/- 5% and 28 +/- 3% during baseline to 0 +/- 4% and -1 +/- 1% following the respective inhibitors. Following administration of the cyclooxygenase inhibitor indomethacin (5 mg/kg i.v.), the CO2 response was converted from vasodilation, 31 +/- 6%, to constriction, -4 +/- 1% (p less than 0.001), while the lipoxygenase inhibitor nordihydroguaiaretic acid (2 mg/kg i.v. or 10(-4) M in CSF) augmented the pial arteriolar response to CO2 from 21 +/- 4% to 34 +/- 7% (p less than 0.005). Topical application of superoxide dismutase (40 units/ml CSF) plus catalase (40 units/ml CSF) also appeared to augment the CO2 response. Suffusion of the cortical surface with acidic CSF at constant PCO2 increased pial arteriolar diameter by 11 +/- 2% that was also abolished by indomethacin. Vasodilatory responses to topical adenosine and theophylline were not affected by indomethacin, suggesting specificity for H+ ion-related vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Changes in pH and PCO2 on Wall Tension in Isolated Rat Intrapulmonary Arteries

“…The magnitude of the relaxation was very similar to that which we observed previously in phenylephrine preconstricted aortic rings (Sweeney et al 1998a) and is in agreement with the widely reported relaxant effect of acidosis in systemic vessels (Tobian et al 1959;Kontos et al 1977a,b;Wagerle & Mishra, 1988;Nielsen et al 1991;Austin & Wray, 1993;Fukuda et al 1993;Wagerle & Degiulio, 1994;Tian et al 1995;Peng et al 1998). In isohydric hypercapnia, however, the tension in PGF2á preconstricted carotid arteries was unchanged.…”

Response of Cerebral Blood Volume to Changes in Arterial Carbon Dioxide Tension in Preterm and Term Infants

“…The direct action of C 0 2 and various other mediators, such as perivascular pH and bicarbonate ion, on the cerebral vessel wall remains controversial, and prostanoids have been recently implicated (33). Indomethacin, a prostaglandin synthetase inhibitor, has been found to abolish this response in preterm infants (34), as well as in rats (35) and gerbils (36), although not in some other experimental animals (37).…”

Effect of 2-Chloroadenosine on Cerebrovascular Reactivity to Hypercapnia in Newborn Pig

“…Thus, if one assumes that adenosine plays no role in mediating cerebral hypercapnic hyperemia, and vasoactive prostanoids produced secondary to CO2-induced increases in hydrogen ion concentra tions are the predominant mediators (Wagerle and Mishra, 1988;Leffler et al, 1989), then our results indicate that adenosine does not interfere with the prostanoid-based vasodilative mechanism, a possi bility raised by previous studies (Ally et al, 1977). Second, our data suggest that the attenuated or abolished CO2 reactivity occurring during hypoten sion (Harper and Glass, 1965;Wei et al, 1980) and hypoxia (McPherson et al , 1987) occurs indepen dently of the many physiologic actions of adeno sine, since concentrations of this nucleoside are el evated under these conditions (Park et al , 1987Van Wylen et al , 1988).…”

“…A hypercap nia-induced increase in extracellular hydrogen ion concentration is likely to be the initial step of this process (Kontos et aI., 1977), but hydrogen ion may not be the final effector. There is evidence that the hyperemia in newborn animals results from hydro gen ion-stimulated production of vasodilative pros tanoids (Wagerle and Mishra, 1988;Leffler et aI., 1989). The purine metabolite adenosine has also been hypothesized to participate in the mediation of hypercapnic vasodilation, based on studies in which adenosine receptor blockade reduced hypercapnia-stimuli was inversely proportional to vessel size.…”