Responses of the basilar artery to products released by platelets during chronic hypertension

The goal of this study was to determine whether responses of the basilar artery to products released by platelets are altered during chronic hypertension. The diameter of the basilar artery was measured using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (6-8 months old) in response to adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue, U-46619. Dilatation of the basilar artery in response to nitroglycerin was also examined in WKY and SHR. Topical application of ADP (10 and 100 microM) produced only minimal changes in diameter of the basilar artery in WKY (3 +/- 1% and 1 +/- 1%, respectively) and SHR (-0.5 +/- 2% and -2 +/- 3%, respectively) (P greater than 0.05 vs WKY). Nitroglycerin, however, produced potent vasodilatation in WKY and SHR. Constriction of the basilar artery in response to serotonin was potentiated in SHR compared to WKY. Serotonin (0.1 and 1.0 microM) constricted the basilar artery by 11 +/- 2% and 20 +/- 2%, respectively, in WKY and by 29 +/- 3% and 40 +/- 3%, respectively, in SHR (P less than 0.05 vs WKY). In contrast, the thromboxane analogue (U-46619) (0.1 and 1.0 microM) produced similar constriction of the basilar artery in WKY (13 +/- 1% and 18 +/- 2%, respectively) and in SHR (14 +/- 3% and 21 +/- 6%, respectively). Thus, augmented vasoconstriction during chronic hypertension was specific for serotonin. Next, we examined the role of the cyclooxygenase pathway in responses of the basilar artery to ADP and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of diabetes mellitus on flow-mediated and endothelium-dependent dilatation of the rat basilar artery.

BACKGROUND AND PURPOSE: Diabetes mellitus may impair endothelium-dependent responses in cerebral arterioles. The basilar artery dilates in response to increases in blood flow. The goal of this study was to examine effects of diabetes mellitus on "flow-mediated" and endothelium-dependent dilatation of the basilar artery. METHODS: Diabetes was induced in rats with 50 mg/kg streptozotocin. Six months later, vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in anesthetized rats under baseline conditions and during occlusion of the carotid arteries. Changes in vessel diameter were also measured during topical application of acetylcholine and sodium nitroprusside. RESULTS: With aortic pressure maintained at baseline levels, blood flow velocity through the basilar artery increased similarly in control and diabetic rats during unilateral common carotid artery occlusion and during bilateral occlusion. In control and diabetic rats, diameter of the basilar artery increased by 10 +/- 2% and 10 +/- 4% during unilateral occlusion and by 27 +/- 5% and 31 +/- 4% during bilateral occlusion, respectively. Thus, diabetes did not impair flow-mediated dilatation of the basilar artery. In contrast, dilatation in response to 10(-5) M topical acetylcholine was less in diabetic rats (13 +/- 2%) than in control rats (45 +/- 8%) (p less than 0.05). Dilator responses to nitroprusside were not impaired by diabetes. CONCLUSIONS: The findings suggest that diabetes produces impairment of endothelium-dependent responses to acetylcholine, but not flow-mediated dilatation, in the basilar artery.     

Perivascular blood attenuates noradrenergic but not cholinergic effects on piglet pial arterioles

We examined the chronic and acute effects of perivascular blood on cerebrovascular responses to norepinephrine and acetylcholine in 35 piglets. In the chronic experiment, fresh autologous blood (n = 15) or cerebrospinal fluid (n = 14, control) was placed under the dura mater over the parietal cortex, and the piglets were allowed to recover from anesthesia. One to 4 days later, a closed cranial window was placed over the parietal cortex and baseline pial arteriolar responses and responses to topical application of the neurotransmitters norepinephrine (10(-6) and 10(-4) M) and acetylcholine (10(-4) M) were determined. We also sampled cerebrospinal fluid from under the window during baseline conditions and during application of the neurotransmitters, and we measured the concentrations of prostanoids (6-ketoprostaglandin F1 alpha, thromboxane B2, prostaglandin F2 alpha, and prostaglandin E2) via radioimmunoassay. Pial arterioles in the chronic control group (n = 13) constricted by 20 +/- 2% (mean +/- SEM) in response to 10(-4) M norepinephrine and by 28 +/- 2% in response to 10(-4) M acetylcholine. In the chronic blood group (n = 14), pial arterioles did not constrict significantly in response to 10(-4) M norepinephrine but constricted normally (23 +/- 4%) in response to 10(-4) M acetylcholine. In the acute experiment, six other piglets had blood placed on the brain surface for 30 minutes and then removed; pial arterioles constricted by 21 +/- 1% in response to 10(-4) M norepinephrine (n = 5) and by 28 +/- 4% in response to 10(-4) M acetylcholine (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of the basilar artery in regulation of blood flow to the brain stem in rats

Large arteries contribute to the regulation of cerebral blood flow. The goal of this study was to examine the effects of changes in diameter of the basilar artery on blood flow to the brain stem. We measured blood flow with laser-Doppler flowmetry in anesthetized rats. The topical application of 10(-6) M serotonin, which selectively constricts large arteries, reduced diameter of the basilar artery by 47 +/- 5% (mean +/- SEM, n = 6) but did not alter blood flow to the ventral brain stem (change in blood flow -2 +/- 5%). The topical application of 10(-8) M vasopressin, which affects both large and small vessels, decreased blood flow by 33 +/- 4% (n = 6). In rats with spontaneous vasomotion, the basilar artery showed rhythmic changes in diameter at a frequency of 4.0 +/- 0.1 cycles/min and an amplitude of 20 +/- 1% of mean diameter (n = 6). Blood flow to the ventral brain stem cycled at the same frequency as and in phase with changes in diameter of the basilar artery, with an amplitude of 15 +/- 1%. We conclude that constriction of the basilar artery may occur with no change in brain stem perfusion. The distinct changes in blood flow during spontaneous vasomotion suggest that vasomotion occurs in intraparenchymal arterioles as well as in the basilar artery.     

Effect of diabetes mellitus on responses of the basilar artery in rats to products released by platelets.

BACKGROUND AND PURPOSE: Aggregation and adherence of platelets to vascular endothelium are increased during diabetes mellitus, and thus responses of cerebral arteries to products released by platelets may have important implications for the pathogenesis of stroke during diabetes. The goal of this study was to determine whether responses of the basilar artery to products released by platelets are altered during diabetes. METHODS: A craniotomy was performed over the ventral medulla to expose the basilar artery. Diameter of the basilar artery was measured using intravital microscopy in nondiabetic and diabetic (50-60 mg/kg i.p. streptozotocin) rats in response to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619. RESULTS: Topical application of 10 and 100 microM adenosine 5'-diphosphate produced only minimal changes in diameter of the basilar artery that were similar in nondiabetic and diabetic rats (p greater than 0.05). At 0.01, 0.1, and 1.0 microM serotonin produced dose-related constriction of the basilar artery that was similar in nondiabetic and diabetic rats (p greater than 0.05). At 0.1 and 1.0 microM U-46619 also produced similar dose-related constriction of the basilar artery in nondiabetic and diabetic rats (p greater than 0.05). CONCLUSIONS: These findings suggest that responses of the basilar artery to products released by platelets are not altered by diabetes mellitus. Thus, it does not appear that alterations in reactivity of the basilar artery to products released by platelets contribute to the pathogenesis of stroke during diabetes.     

Effect of the thromboxane A2 mimetic U 46619 on pial arterioles of rabbits and rats

Our previous experiments have shown that thromboxane A2 is a strong contractor of cerebral arterial smooth muscle strips. The objective of these experiments was to determine if U 46619, a stable thromboxane A2 mimetic, affects the cerebral microcirculation in vivo. Pial arteriole diameter in rabbits and rats was measured with a microscope using the closed cranial window technique. Topical application of 10(-11) to 10(-6) M U 46619 induced dose-dependent arteriole vasoconstriction in both species. In rabbits and rats the maximum vasoconstriction was 9.7 +/- 1.3% (mean +/- SEM) and 14.0 +/- 0.5%, respectively. In rats, 10(-7) and 10(-6) M U 46619 induced intravascular platelet aggregation accompanied by a further decrease in diameter and transient occlusion of the arterioles and venules. U 46619 had no significant effect on rabbit pial arterioles that were predilated by hypercapnia or hypercapnia plus hypoxia. Our data suggest that in animals with a normal vasculature, thromboxane A2 may be a moderate constrictor of cerebral arterioles and that this constrictor effect is prevented by hypercapnia and hypoxia.     

Exogenous norepinephrine constricts cerebral arterioles via alpha 2-adrenoceptors in newborn pigs

The purpose of this study was to determine whether exogenous norepinephrine mediates cerebrovascular constriction via alpha 1- or alpha 2-adrenoceptors in anesthetized neonatal pigs. Diameters of pial arterioles in anesthetized piglets, 1--6 days old, were investigated using a "closed" cranial window. We examined constrictor effects of norepinephrine on pial arterioles in the absence and presence of relatively selective alpha 1-(prazosin) and alpha 2-(yohimbine) adrenoceptor antagonists (1 mg/kg i.v.). Yohimbine and prazosin inhibited pial arteriolar constriction induced by topical application of clonidine and phenylephrine (10(-6) and 10(-4) M, respectively), and yohimbine did not affect the response to topical phenylephrine. In one group diameter was 188 +/- 13 (mean +/- SEM) micron during control and 146 +/- 12 micron during 10(-5) M norepinephrine (22 +/- 5% constriction). Following yohimbine the same vessels did not constrict significantly. In another group 10(-5) M norepinephrine constricted arterioles by 22 +/- 5%, and this response was unaffected by prazosin (24 +/- 5% constriction). We conclude that pial arterioles are responsive to both alpha 1- and alpha 2-adrenoceptor agonists, that intravenous administration of prazosin and yohimbine results in these drugs crossing the blood-brain barrier and inhibiting constrictor effects of agonists, and that norepinephrine constricts pial arterioles predominantly via alpha 2-adrenoceptors.     

Effects of cocaine on pial arterioles in cats

We used the closed cranial window technique to observe the responses of pial arterioles to topical application of cocaine in 29 anesthetized cats. Alterations in arteriolar diameter were dependent on the concentration of cocaine applied. Cocaine dissolved in artificial cerebrospinal fluid at concentrations of 10(-8) or 10(-7) M was without effect. Concentrations of 10(-6) and 10(-5) M produced dilation (4.9 +/- 1.5% [mean +/- SEM] and 5.9 +/- 2.0%, respectively) in large arterioles (greater than 100 microns) but no significant change in the diameter of small arterioles (less than 100 microns). A concentration of 10(-4) M dilated both large and small arterioles (20.3 +/- 3.1% and 12.0 +/- 7.1%, respectively). Pretreatment with 1 mg/kg i.v. propranolol blocked the increase in pial arteriolar diameter after application of 10(-4) M cocaine and produced significant vasoconstriction in small arterioles (-8.3 +/- 3.1%). Cocaine produces vasodilation of cat cerebral arterioles. This effect appears to be mediated, at least in part, by mechanisms that depend on stimulation of beta-adrenergic receptors.     

Reactivity of rat pial arterioles and venules to adenosine and carbon dioxide: with detailed description of the closed cranial window technique in rats

This study describes a closed cranial window technique that allows the observation and measurement of rat pial arterioles and venules in situ. The resolving power of this system is 1-2 microns. Using this sensitive technique, we characterized the responses to 7% carbon dioxide inhalation and adenosine in arterioles (10-70 microns) and venules (15-100 microns). During carbon dioxide inhalation, larger arterioles (greater than 40 microns) dilated more than smaller arterioles (less than 20 microns). There was limited vasoreactivity of pial venules during CO2 inhalation. Dilation of arterioles was initially observed with an adenosine concentration of 10(-8) M. Almost a twofold increase in diameter was noted at 10(-3) M. In contrast to the effect of CO2 inhalation, the degree of dilation with topical application of adenosine was not size dependent. Pial venules did not respond to adenosine. The technique for observation of pial vessels using the closed cranial window and for measurement of vessel diameter by video camera system microscopy is a powerful tool for studying in vivo the cerebral circulation in the rat.     

Atherosclerosis potentiates constrictor responses of cerebral and ocular blood vessels to thromboxane in monkeys

The goal of our study was to examine the effects of infusion of serotonin and the thromboxane A2 analogue U46619 into one carotid artery to stimulate their release from platelets during aggregation. We measured blood flow to the brain and eye using microspheres and cerebral microvascular pressure in the pial arteries of normal and atherosclerotic cynomolgus monkeys. Unilateral intracarotid infusion of 10-30 micrograms/min serotonin did not affect cerebral blood flow in normal or atherosclerotic monkeys; serotonin did not alter blood flow to the eye in normal monkeys but decreased flow to the retina and choroid in atherosclerotic monkeys by 39 +/- 11% and 44 +/- 10% (mean +/- SEM), respectively. Infusion of 30 ng/min U46619 did not alter cerebral blood flow but increased the pressure gradient from the aorta to the pial artery, which is an index of large-artery resistance, in atherosclerotic monkeys. U46619 had no effect on blood flow to the eye in normal monkeys but decreased blood flow to the retina and choroid by 71 +/- 14% and 53 +/- 13%, respectively, in atherosclerotic monkeys. Thus, atherosclerosis potentiates the constrictor responses of large cerebral arteries to thromboxane and the responses of blood vessels of the eye to thromboxane and serotonin.     

Purine catabolites and pial arteriolar diameter in transient cerebral ischemia]

In transient cerebral ischemia, extracellular purine catabolites and pial arteriolar diameter were measured continuously. Ischemia during one hour was induced by unilateral occlusion of left middle cerebral artery in feline. Extracellular purine catabolites were sampled by in vivo brain microdialysis technique from the gray matter at ectosylvian gyrus. These catabolites were analyzed by HPLC system. Simultaneously, reactivity of pial arteriole was observed and its diameter was measured through the cranial window using intravital microscope and width analyzer. Extracellular concentrations of adenosine, inosine, hypoxanthine and xanthine were found to be 0.80 +/- 0.16 microM, 2.01 +/- 0.95 microM, 4.01 +/- 2.73 microM and 3.93 +/- 2.39 microM, respectively. During ischemia, the concentration of adenosine increased 8.7-fold and arteriolar diameter was 170% of the resting state. These findings in extracellular adenosine concentration and pial arteriolar diameter during ischemia support a role of adenosine in regulation of cerebral blood flow. After reperfusion, arteriolar diameter had returned to 120% of the resting state. But 50 min after reperfusion, pial arteriole began to dilate again coincident with the peak of xanthine concentration. These results suggest that free radicals were produced and could affect pial arterioles 50 min after reperfusion.     

Effect of 2-chloroadenosine on cerebrovascular reactivity to hypercapnia in newborn pig.

The effect of local administration of vasodilative concentrations of the adenosine receptor agonist 2-chloroadenosine (2-CADO) on the hyperemic responses of the pial and parenchymal microcirculations to graded hypercapnia was determined. The cranial window and brain microdialysis-hydrogen clearance techniques were utilized in two groups of isoflurane-anesthetized newborn pigs to measure changes in pial diameters and local CBF, respectively, in response to graded hypercapnia in the absence and presence of 2-CADO. Progressive size-dependent dilations of pial arterioles [small = 41 +/- 7 microns (mean +/- SD), intermediate = 78 +/- 13 microns, and large = 176 +/- 57 microns in diameter] occurred in response to graded hypercapnia alone (PaCO2 = 58 and 98 mm Hg) and to superfusions of 2-CADO (10(-5) M) during normocapnia; the magnitude of the dilative response to each of these stimuli was inversely proportional to vessel size. When hypercapnia was induced concomitantly with 2-CADO superfusion, the dilative effects of each stimulus were directly additive. Similarly, local microdialysis infusion of 10(-5) M 2-CADO, which doubled CBF during normocapnia, did not affect the hyperemic response of the parenchymal circulation to graded hypercapnia (PaCO2 = 69 and 101 mm Hg). Our findings are consistent with the participation of adenosine in the mediation of cerebral hypercapnic hyperemia. If, however, adenosine is not involved in this dilative response, our results indicate that concomitant vascular and neuromodulatory actions induced by adenosine receptor stimulation do not affect the mechanism responsible for the hypercapnic hyperemic response.     

Plasminogen activators contribute to age-dependent impairment of NMDA cerebrovasodilation after brain injury

Previous studies have observed that fluid percussion brain injury (FPI) impaired NMDA induced pial artery dilation in an age-dependent manner. This study was designed to investigate the contribution of plasminogen activators to impaired NMDA dilation after FPI in newborn and juvenile pigs equipped with a closed cranial window. In the newborn pig, NMDA (10(-8), 10(-6) M) induced pial artery dilation was reversed to vasoconstriction following FPI, but pretreatment with the plasminogen activator inhibitor PAI-1 derived hexapeptide (EEIIMD) (10(-7) M) prevented post injury vasoconstriction (9 +/- 1 and 16 +/- 1, vs. -6 +/- 2 and-11 +/- 3, vs. 5 +/- 1 and 9 +/- 1% for responses to NMDA 10(-8), 10(-6) M prior to FPI, after FPI, and after FPI in EEIIMD pretreated animals, respectively). In contrast, in the juvenile pig, NMDA dilation was only attenuated following FPI and EEIIMD pretreatment partially prevented such inhibition (9 +/- 1 and 16 +/- 1 vs. 2 +/- 1 and 4 +/- 1 vs. 5 +/- 1 and 7 +/- 1% for responses to NMDA prior to FPI, after FPI, and after FPI in EEIIMD pretreated animals, respectively). Additionally, EEIIMD blunted age-dependent pial artery vasoconstriction following FPI. EEIIMD blocked dilation to the plasminogen activator agonists uPA and tPA while responses to SNP and papaverine were unchanged. Pretreatment with suPAR, which blocked dilation to uPA, elicited effects on pial artery diameter and NMDA vascular activity post FPI similar to that observed with EEIIMD. These data show that EEIIMD and suPAR partially prevented FPI induced alterations in NMDA dilation and reductions in pial artery diameter. EEIIMD and suPAR are efficacious and selective inhibitors of plasminogen activator induced dilation. These data suggest that plasminogen activators contribute to age-dependent impairment of NMDA induced dilation following FPI.     

Mechanisms of impaired endothelium-dependent cerebral vasodilatation in response to bradykinin in hypertensive rats

Bradykinin produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats than in normotensive Wistar-Kyoto rats. The goals of this study were to determine the mediator of bradykinin-induced dilatation in cerebral arterioles of rats and to determine whether responses to this mediator are altered in hypertensive rats. Diameter of pial arterioles (20-65 microns) was measured using intravital microscopy in 18 normotensive and 17 hypertensive rats. Superfusion of 3 x 10(-7) M bradykinin dilated pial arterioles by 53 +/- 4% (mean +/- SEM) in normotensive rats but only 33 +/- 6% in hypertensive rats (p less than 0.05 versus normotensive rats). Vasodilatation in response to bradykinin was almost completely inhibited by 280 units/ml catalase in both normotensive and hypertensive rats (n = 7 and n = 7, respectively) whereas 150 units/ml superoxide dismutase (n = 6 and n = 5, respectively) and 1 mM deferoxamine (n = 5 and n = 5, respectively) did not attenuate bradykinin-induced vasodilatation. These findings suggest that hydrogen peroxide is the mediator of bradykinin-induced dilatation in cerebral arterioles of rats. We also examined responses of cerebral arterioles to hydrogen peroxide in five normotensive and six hypertensive rats. Dilator responses of cerebral arterioles to 3.2 x 10(-5) M to 1.6 x 10(-4) M hydrogen peroxide did not differ in normotensive and hypertensive rats, which suggests that impaired dilatation of cerebral arterioles in response to bradykinin is not related to altered responsiveness of smooth muscle to an endothelium-derived relaxing factor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelium-derived relaxing factor modulates noradrenergic constriction of cerebral arterioles in rabbits.

BACKGROUND AND PURPOSE: Cerebral arterioles are relatively unresponsive to norepinephrine. We tested the hypothesis that release of endothelium-derived relaxing factor is stimulated by norepinephrine and attenuates adrenergic constriction of pial arterioles. METHODS: In seven anesthetized New Zealand White rabbits, diameter of pial arterioles was measured through a cranial window. Responses to topical application of norepinephrine and arginine vasopressin were examined before and during application of NG-nitro-L-arginine, which inhibits synthesis of endothelium-derived relaxing factor. RESULTS: Norepinephrine (10(-6) M) had no effect (0 +/- 3%, mean +/- SE) on arteriolar diameter under basal conditions. Norepinephrine decreased arteriolar diameter by 15 +/- 4% during application of nitro-L-arginine (10(-4) M) (p less than 0.05 versus basal response). L-arginine inhibited the effect of nitro-L-arginine on responses of pial arterioles to norepinephrine. In contrast to norepinephrine, constrictor responses of pial arterioles to vasopressin were not potentiated by nitro-L-arginine. CONCLUSIONS: Norepinephrine, but not arginine vasopressin, releases endothelium-derived relaxing factor, which inhibits constrictor responses of cerebral arterioles in rabbits. This mechanism contributes to the finding that cerebral vessels in rabbits are relatively unresponsive to noradrenergic stimuli.     

G protein activation elicits cerebrovasodilation through interaction with K(ATP) and K(Ca) channels

This study was designed to characterize the vascular activity of two activators of a pertussis toxin-sensitive G protein, mastoparan and mastoparan-7, on pial artery diameter and their interaction with the ATP sensitive K (K(ATP)) and calcium sensitive K (K(Ca)) channel in newborn pigs equipped with a closed cranial window. Mastoparan (10(-8), 10(-6) M) elicited pial artery dilation that was blunted by the K(ATP) channel antagonist glibenclamide (10(-6) M) and attenuated by the K(Ca) channel antagonist iberiotoxin (10(-7) M) (10+/-1 and 17+/-1 vs. 3+/-1 and 6+/-1 vs. 6+/-1 and 10+/-2% for mastoparan in the absence and presence of glibenclamide or iberiotoxin, respectively). Similar results were observed for mastoparan-7 but the inactive analogue mastoparan-17 had no effect on pial artery diameter. These data show that G protein activation elicits cerebrovasodilation through interaction with K(ATP) and K(Ca) channels.     

Does vasospasm occur in small pial arteries and arterioles of rabbits?

BACKGROUND: Vasospasm is a serious complication associated with subarachnoid hemorrhage. Successful management of vasospasm will ultimately depend on a clear understanding of the scope of this phenomenon, including whether arterial elements of different calibers are equally affected. We therefore examined the responses to subarachnoid hemorrhage in rabbit basilar arteries, small pial arteries, and arterioles. SUMMARY OF REPORT: We compared the brain stem pial arteries of 10 perfusion-fixed male New Zealand White rabbits after experimental subarachnoid hemorrhage to those of five control rabbits using morphological analysis of cross-sections of plastic-embedded vessels. After subarachnoid hemorrhage, the internal elastic lamina was highly corrugated in all basilar arteries (mean diameter 319 +/- 51 microns). These arteries were severely constricted in comparison with the control group, in which the mean diameter was 691 +/- 17 microns, and corrugation of the internal elastic lamina was not present. In contrast, small pial arteries and arterioles very rarely demonstrated a vasoconstrictive configuration after subarachnoid hemorrhage. The contractility of the smaller vessels was confirmed by injecting 2 mg/kg BaCl2 intracisternally. Following BaCl2 injection, corrugation of the internal elastic lamina was detected in the small arteries and arterioles as well as the basilar arteries. CONCLUSIONS: We conclude that experimental chronic vasospasm after subarachnoid hemorrhage in rabbits tends to occur in large conducting arteries rather than in smaller pial arteries and arterioles.     

The effects of dipyridamole and theophylline on rat pial vessels during hypocarbia

Hypocarbia results in an increase in brain adenosine concentrations, presumably because of brain hypoxia associated with hypocarbic vasoconstriction. It was hypothesized that adenosine limits the degree of hypocarbic vasoconstriction. To test this hypothesis, the effects of dipyridamole and theophylline on CO2 reactivity during hypocarbia were investigated in anesthetized rats. Dipyridamole should reduce the vasoconstriction by potentiating adenosine action, whereas theophylline should increase the vasoconstriction by blocking adenosine receptors. Cortical pial arterioles of mechanically ventilated and anesthetized rats were displayed on a video monitor system through a closed cranial window. Arterial blood pressure and oxygen tension were stable. CO2 reactivity, formulated as 100 X [delta diameter (micron)/resting diameter (micron)]/delta PaCO2 (mmHg), in the hypocarbic phase was calculated before and after topical superfusion of dipyridamole (10(-6) M; n = 7) and theophylline (5 X 10(-5) M; n = 6). CO2 reactivity was significantly decreased after superfusion of dipyridamole (0.57 +/- 0.08; mean +/- SEM) as compared with mock cerebrospinal fluid (CSF) (0.97 +/- 0.17, p less than 0.05, n = 7). On the other hand, CO2 reactivity after superfusion of theophylline was increased (1.63 +/- 0.28) as compared with mock CSF (1.00 +/- 0.20, p less than 0.05, n = 6), indicating that adenosine is involved in hypocarbic vasoconstriction.     

Effects of topical adenosine analogs and forskolin on rat pial arterioles in vivo

We utilized the closed window technique to study the in vivo responses of rat pial arterioles to superfused adenosine agonists. Adenosine and its analogs dilated pial arterioles and exhibited the following order of potency: 5'N-ethylcarboxamide adenosine (NECA) greater than 2-chloroadenosine (2-CADO) greater than adenosine = R-N6-phenylisopropyladenosine (R-PIA) = S-PIA greater than N6-cyclohexyladenosine (CHA). This potency profile suggests that cerebral vasodilation is mediated through the A2 receptor. Forskolin (10(-9) M) potentiated the vasodilation caused by 10(-6) M NECA, thus implicating adenylate cyclase activation during NECA-induced vasodilation and providing further support for involvement of the A2 receptor.     

Selective attenuation by perivascular blood of prostanoid-dependent cerebrovascular dilation in piglets

Cerebral hemorrhagic insults are common in neonates. However, the consequences of intracranial blood on cerebral hemodynamics are poorly understood. We examined the effects of perivascular blood on cerebrovascular dilator responses in 29 piglets. Fresh, autologous blood (n = 15) or cerebrospinal fluid (n = 14) was placed under the dura mater over the parietal cortex, and the piglets were allowed to recover from anesthesia. One to four days later, a closed cranial window was placed over the parietal cortex and pial arteriolar responses to arterial hypercapnia (PaCO2 greater than 55 mm Hg), hemorrhagic hypotension (mean arterial blood pressure less than 35 mm Hg), or topical application of 10(-6) and 10(-4) M isoproterenol were determined. Pial arterioles in the cerebrospinal fluid group dilated 27 +/- 4% (mean +/- SEM) (n = 11) in response to hypercapnia, 26 +/- 5% (n = 9) in response to hypotension, and 26 +/- 3% in response to 10(-6) M and 40 +/- 4% in response to 10(-4) M isoproterenol (n = 11). In the group in which blood was placed on the parietal cortex, pial arterioles did not dilate significantly in response to hypercapnia (8 +/- 3%, n = 11) or hypotension (2 +/- 5%, n = 13) but dilated normally in response to isoproterenol (25 +/- 5% in response to 10(-6) M and 36 +/- 7% in response to 10(-4) M, n = 13). We conclude that prolonged contact of pial arterioles with extravascular blood selectively attenuates cerebrovascular dilation in piglets.