Biomedical subjects

D W Busija

Publications and source records attributed to D W Busija.

At least 109 records · Page 6Linked to original sources

PubMed1989

Postischemic cerebral microvascular responses to norepinephrine and hypotension in newborn pigs.

We examined the effects of 20 minutes' cerebral ischemia on cerebral microcirculatory responses to topical norepinephrine and systemic hypotension in three groups (sham-operated control, 2-3 hours postischemia, and 24 hours postischemia) of anesthetized newborn pigs equipped with closed cranial windows. Cerebral ischemia may eliminate the prostanoid vasodilator system from the cerebral circulation. Norepinephrine (10(-4) M) decreased pial arteriolar diameters similarly in all three groups (27%, 28%, and 21%, respectively), but only the sham-operated group exhibited pial arteriolar dilation in response to hypotension (28% at 33 mm Hg). Two-three and 24 hours after cerebral ischemia, hypotension decreased pial arteriolar diameters (21% and 17%, respectively). In sham-operated piglets, norepinephrine and hypotension increased cortical periarachnoid cerebrospinal fluid prostanoid concentrations. However, neither norepinephrine nor hypotension altered cerebral prostanoid production 2-3 or 24 hours after cerebral ischemia. Therefore, we conclude that after cerebral ischemia, autoregulatory pial arteriolar dilation in response to hypotension is absent, while vasoconstriction in response to norepinephrine is intact.

Administration, Topical↗

PubMed1989

Ischemia alters cerebral vascular responses to hypercapnia and acetylcholine in piglets.

Effects of ischemia (20 min) on cerebral cortical prostanoid synthesis and microvascular responses to hypercapnia and topical acetylcholine were examined in anesthetized newborn pigs. Pial arteriolar dilation in response to hypercapnia (10% CO2 ventilation, 10 min) was absent 2 h after ischemia and reversed toward constriction by 24 h postischemia. In sham control piglets, hypercapnia increased cortical periarachnoid fluid prostanoid concentrations. After ischemia, hypercapnia did not affect prostanoid concentrations on the brain surface. Acetylcholine (10(-3) M)-induced pial arteriolar constriction was reversed toward dilation 24 h after cerebral ischemia. Further, acetylcholine-induced prostanoid synthesis was markedly attenuated after ischemia. We conclude that cerebral ischemia-reperfusion alters cerebral prostanoid synthesis and microvascular control in newborn pigs. These abnormalities persist for at least 24 h.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Influence of intraarterial norepinephrine on cerebral hemodynamics of newborn pigs.

Effects of intraarterial norepinephrine on cerebral hemodynamics were investigated in conscious newborn pigs. Intracarotid infusion of norepinephrine (100 ng/min) increased cerebral blood flow from 72 +/- 5 to 82 +/- 8 ml/100 g.min. The norepinephrine-induced increase in cerebral blood flow was accompanied by an increase in cerebral oxygen consumption from 2.75 +/- 0.17 to 3.11 +/- 0.29 ml O2/100 g.min. Both the increase in cerebral oxygen consumption and the increase in cerebral blood flow were blocked by propranolol and unchanged by combined prazosin and yohimbine treatment. These data show that intraarterial norepinephrine increases cerebral blood flow and cerebral oxygen consumption in newborn pigs. beta-Adrenergic stimulation increases cerebral oxygen consumption. This increase may produce the increase in cerebral blood flow caused by the norepinephrine.

Animals↗

PubMed1989

Permissive role of prostanoids in acetylcholine-induced cerebral vasoconstriction.

The present study was designed to test the hypothesis that prostanoids play a permissive role in acetylcholine-induced cerebral constriction. Pial arterioles of newborn pigs were observed using a closed cranial window. Pial arteriolar constriction induced by topical acetylcholine (10(-5) M) was blocked by indomethacin (5 mg/kg i.v.), but was restored when acetylcholine was coadministered with topical prostaglandin (PG) F2 alpha (1 ng/ml), U46619 (1 ng/ml) or PGH2 (100 ng/ml). The restored acetylcholine response was blocked by topical pirenzepine (10(-3) M), a muscarinic-1 antagonist. Constriction and ability of all three prostanoids to restore acetylcholine-induced constriction was blocked by SQ 29,548 (10(-4) M), a purported thromboxane A2/PGH2 receptor antagonist. Subthreshold concentrations of U46619 and PGF2 alpha (0.1 ng/ml) restored acetylcholine-induced constriction, whereas threshold and subthreshold concentrations of PGE2, platelet-activating factor and norepinephrine had no effect. Therefore, activation of the thromboxane A2/PGH2 receptor appears to be necessary for acetylcholine-induced constriction to occur. Thus, prostanoids appear to play a permissive role in acetylcholine-induced pial arteriolar constriction in newborn pigs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1989

Effects of hypertension and sympathetic denervation on cerebral blood flow in newborn pigs.

To investigate the potential role of sympathetic nerves in preventing pronounced increases in cerebral blood flow, we evaluated the effects of abrupt hypertension on the cerebral circulation of newborn pigs with intact cerebral sympathetic innervation and after cerebral sympathetic denervation. Epinephrine infusion was used to induce abrupt increases in mean (+/- SEM) arterial pressure (innervated pigs, 62 +/- 3 mm of Hg to 115 +/- 3 mm of Hg; denervated pigs, 71 +/- 4 mm of Hg to 132 +/- 4 mm of Hg) that remained increased for the 3 minutes of the study. Abrupt hypertension increased blood flow to all brain regions. In denervated pigs, the increased flow to the cerebrum was prolonged, compared with that in pigs with intact sympathetic innervation. Differences between pigs of the innervated and denervated groups were not apparent, with respect to blood flow to any other region (caudate region, brain stem, cerebellum). In newborn pigs, sympathetic nerves may attenuate hypertension-induced increases in blood flow to the cerebrum, but do not appear to affect flow to the rest of the brain.

Animals↗

PubMed1988

Acetylcholine dramatically increases prostanoid synthesis in piglet parietal cortex.

We investigated effects of exogenous acetylcholine on prostanoid synthesis by parietal cortex in neonatal pigs. Cerebrospinal fluid (CSF) with no drug, and CSF containing acetylcholine at 10(-6) to 10(-3) M was injected under a 'closed' cranial window, and after 5 min the CSF was collected and analyzed by radioimmunoassay for prostaglandin (PG) E2, PGF2 alpha, PGD2, 6-keto-PGF1 alpha (the hydrolysis product of prostacyclin), and thromboxane (TX) B2 (the hydrolysis product of TXA2). PGE2 and PGF2 alpha were the predominant prostanoids in CSF under control conditions. Levels of all CSF prostanoids increased after topical application of acetylcholine, with the largest increases being for PGE2 and PGF2 alpha. During control conditions, levels were 1294 +/- 170 (mean +/- S.E.M.) pg/ml for PGE2 (n = 16), 1032 +/- 143 pg/ml for PGF2 alpha (n = 3), 659 +/- 92 pg/ml for 6-keto-PGF1 alpha (n = 15), 141 +/- 44 pg/ml for TXB2 (n = 12), and were below detectable levels for PGD2. Following application of 10(-3) M acetylcholine, levels were 34,535 +/- 5438 pg/ml for PGE2, 15,539 +/- 2772 pg/ml for PGF2 alpha, 2967 +/- 547 pg/ml for 6-keto-PGF1 alpha, 580 +/- 105 pg/ml for TXB2, and 556 +/- 221 pg/ml for PGD2. These results suggest that prostanoids could play a role in mediating effects of acetylcholine in the brain, or in modulating acetylcholine release via a negative feedback mechanism.

Acetylcholine↗

PubMed1988

Effect of 15-HETE on cerebral arterioles of newborn pigs.

Effects of topical application of 15-HETE on pial arteriolar diameter and cortical periarachnoid cerebrospinal fluid (CSF) prostanoid concentrations were investigated in chloralose-anesthetized newborn pigs. Pial arteriolar diameters were measured using a closed cranial window, and CSF samples from under the window were collected for prostanoid analysis after applying artificial CSF without drug and CSF containing 15-HETE (1, 10, 100, 10000 ng/ml). 15-HETE caused significant dose-related constriction from 162 +/- 17.0 microns (control diameter) to 136 +/- 14.5 and 129 +/- 18.7 microns (100 and 1000 ng/ml, respectively). The concentration of PGE2 (but not of PGF2 alpha or 6-keto-PGF1 alpha) increased in CSF at 100 and 1000 ng/ml of 15-HETE. Pial arteriolar responses to 15-HETE were determined before and after indomethacin treatment (5 mg/kg, i.v.). 15-HETE (100 ng/ml) constricted pial arterioles before indomethacin (diameter change, -15 +/- 10%); after indomethacin, constriction was potentiated in response to the same dose (diameter change, -26 +/- 7%). These data support the hypothesis that, in newborn piglets, 15-HETE exerts a vasoconstrictor effect on pial arterioles, which appears to be attenuated by 15-HETE-induced stimulation of dilator prostanoids.

Animals↗

PubMed1988

Adrenergic and prostanoid mechanisms in control of cerebral blood flow in hypotensive newborn pigs.

The interaction between adrenergic and prostanoid mechanisms in the control of cerebral hemodynamics in the conscious, hypotensive newborn pig was investigated. Pretreatment with the selective alpha 1- and alpha 2-adrenoceptor antagonists prazosin and yohimbine, respectively, had no effect on cerebral blood flow, calculated cerebral vascular resistance, or cerebral metabolic rate either before or after hemorrhagic hypotension. Indomethacin treatment (5 mg/kg ia) of piglets following hemorrhage caused a significant decrease in blood flow to all brain regions within 20 min. This decrease in cerebral blood flow resulted from increased cerebral vascular resistances of 54 and 177%, 20 and 40 min after treatment, respectively. Cerebral oxygen consumption was reduced from 2.42 +/- 0.28 to 1.45 +/- 0.28 ml.100 g-1.min-1 and to 1.0 +/- 0.28 ml.100 g-1.min-1 20 and 40 min after indomethacin, respectively, in hemorrhaged piglets. Decreases in cerebral blood flow and metabolic rate and increases in vascular resistance on treatment with indomethacin were the same as in animals pretreated with vehicle, prazosin, or yohimbine. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn, as reported previously. These data do not implicate removal of sympathetic modulation by prostanoids as a mechanism for indomethacin-induced cerebral vasoconstriction in hypotensive newborn piglets.

Animals↗

PubMed1988

Histamine dilates pial arterioles of newborn pigs through prostanoid production.

To test the hypothesis that histamine would dilate pial arterioles via a prostanoid mechanism, histamine was placed on the brain surface of anesthetized newborn pigs via a closed cranial window. Pial arteriolar diameters were measured after topical application of 10(-7), 10(-6), 10(-5), 10(-4), and 10(-3) M histamine. In addition, cortical cerebrospinal fluid (CSF) was collected for radioimmunoassay of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TxB2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and prostaglandin F2 alpha (PGF2 alpha). The animals were then randomized to receive either indomethacin trihydrate (5 mg/kg, iv) or an equal volume of saline (vehicle). The protocol then was repeated. Histamine (before indomethacin or vehicle infusion) caused concentration-dependent vasodilation. This vasodilation was accompanied by a significant increase in cortical CSF 6-keto-PGF1 alpha and PGE2. Concentrations of TxB2, PGD2, and PGF2 alpha were not altered significantly by histamine application. Pretreatment with indomethacin blocked the histamine-induced cerebral vasodilation, but vasodilation after vehicle was intact. These data imply that histamine dilates the pial arterioles of newborn pigs by stimulating the synthesis of vasodilator prostanoids.

Animals↗

PubMed1988

Hyperthermia increases cerebral metabolic rate and blood flow in neonatal pigs.

We examined effects of hyperthermia on cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) in anesthetized, newborn pigs (2-5 days old). CBF and CMRO2 were measured during normothermia (38 degrees C) and during hyperthermia induced by body heating (42 degrees C). During normothermia, total CBF was 32 +/- 3 ml.min-1.100 g-1 (n = 9), and CMRO2 was 1.34 +/- 0.08 ml O2.100 g-1.min-1 (n = 7). During hyperthermia, total CBF increased by 97 +/- 23% and CMRO2 by 65 +/- 24%. We also examined whether cerebral resistance vessels were responsive under these conditions. During hyperthermia, total CBF was 63 +/- 6 ml.min-1.100 g-1, and CMRO2 was 2.13 +/- 0.27 ml O2.100 g-1.min-1. During sustained hyperthermia, intravenous injection of 5 mg/kg of indomethacin decreased total CBF by 45 +/- 7% (n = 9), and CMRO2 fell by 55 +/- 10% (n = 5). We conclude that 1) hyperthermia increases CBF and CMRO2, and 2) the dilated cerebrovascular bed during hyperthermia still is responsive to a constrictor stimulus.

Animals↗

PubMed1988

Postischemic generation of superoxide anion by newborn pig brain.

Cerebral superoxide anion generation during reperfusion after total cerebral ischemia was measured in newborn pigs. Superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined using two closed cranial windows inserted over the parietal cortices. Twenty minutes of total cerebral ischemia was produced by increasing intracranial pressure, and SOD-inhibitable NBT reduction was determined during 20 min of reperfusion. SOD-inhibitable NBT reduction (8.7 +/- 1.5 pmol.mm-2.20 min-1) was greater in piglets subjected to cerebral ischemia followed by reperfusion than in control piglets not exposed to ischemia (1.6 +/- 1.3 pmol.mm-2.20 min-1). Pretreatment with indomethacin (5 mg/kg iv) markedly reduced postischemia SOD-inhibitable NBT reduction (2.8 +/- 1.1 pmol.mm-2.20 min-1). We conclude that superoxide anion radical is produced by newborn pig brain during postischemic reperfusion. Furthermore, cyclooxygenase metabolism of arachidonic acid appears to be a major source of this activated oxygen during reperfusion of ischemic piglet brain.

Animals↗

PubMed1988

Platelet activating factor: a potent constrictor of cerebral arterioles in newborn pigs.

This study characterized the nature of the response to platelet activating factor (PAF) in the cerebral microcirculation of the newborn pig. Pial arterioles were observed directly using a closed cranial window in chloralose-anesthetized piglets. Topical application of 10-100 ng/ml PAF produced dose-dependent decreases in pial arteriolar diameter; diameters were 193 +/- 27 microns for control, 167 +/- 25 microns at 10 ng/ml, and 129 +/- 21 microns at 100 ng/ml. Topical application of 30-300 ng/ml norepinephrine and 3-30 ng/ml U46619, a purported thromboxane A2 receptor agonist, also produced dose-dependent decreases in pial arteriolar diameter. After topical administration of U66985 (1 microgram/ml), a putative PAF antagonist, responses to PAF were attenuated significantly, but responses to norepinephrine and U46619 were unchanged. Moreover, intravenously administered U66985 (0.1 mg/kg) antagonized PAF responses as well. Responses to PAF were unchanged after cyclooxygenase and leukotriene receptor inhibition. Further, PAF did not increase cortical subarachnoid cerebrospinal fluid prostaglandin or leukotriene levels. These data indicate that PAF is a potent constrictor of cerebral arterioles in newborn pigs and that its mechanism of action is independent of formation of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. These data also suggest that U66985 may be a selective PAF antagonist that crosses the blood-brain barrier. Since PAF is an endogenous lipid released from a variety of tissues and may be an important mediator of inflammation and allergic reaction, PAF could be involved in the pathophysiology of the cerebral circulation in the perinatal period.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1988

Indomethacin restricts cerebral blood flow during pressure ventilation of newborn pigs.

Unanesthetized newborn pigs were studied to evaluate the immediate (10 min) and delayed (45 min) effects of increased ventilation pressure coupled with cyclooxygenase inhibition. Cardiac output and cerebral blood flow were measured at a low (5 cm H2O) and high (30 cm H2O) mean airway pressure (Paw) before and 45 min after 5 mg/kg of indomethacin. In a second group, these parameters were also measured 10 min after indomethacin was given during ventilation at a Paw of 30 cm H2O. Before treatment with indomethacin, increasing Paw decreased cardiac output without affecting cerebral blood flow. Baseline (Paw = 5 cm H2O) cerebral blood flow decreased 40% 45 min after indomethacin treatment. Adding the stress of a ventilation-induced drop in cardiac output did not further depress cerebral blood flow. When indomethacin was administered during high Paw, cerebral blood flow decreased markedly within 10 min. Cerebral oxygen consumption was maintained by increasing oxygen extraction. Therefore, indomethacin decreases cerebral blood flow at a high Paw. The fall in cerebral blood flow decreases brain oxygen delivery. However, cerebral oxygen consumption is maintained by an increase in oxygen extraction.

Animals↗

PubMed1988

Acetylcholine produces cerebrovascular constriction through activation of muscarinic-1 receptors in the newborn pig.

This study was designed to characterize the nature of responses to selective muscarinic (M)-1 and M-2 agonists and to determine the receptor subtype which mediates the vascular response to acetylcholine in the cerebral circulation of the newborn pig. Pial arterioles of anesthetized newborn pigs were observed using the closed cranial window method. Topical McN-A-343 (10(-7), 10(-4) M), an M-1 agonist, produced pial arteriolar constriction (diameters were 140 +/- 8, 127 +/- 9 and 111 +/- 8 microns for control, 10(-7) and 10(-4) M McN-A-343) that was blocked by topical pirenzepine (10(-3) M), an M-1 antagonist. Topical bethanachol (10(-7), 10(-4) M), an M-2 agonist, produced pial arteriolar dilation (diameters were 148 +/- 8, 169 +/- 10 and 181 +/- 10 microns for control, 10(-7) and 10(-4) M bethanachol) that was blocked by 4-DAMP 4-diphenylacetoxy-N'-methylpiperidine methiodide (10(-3) M), an M-2 antagonist. Responses to McN-A-343 were unchanged after 4-DAMP, and responses to bethanachol were unchanged after pirenzepine. Topical McN-A-343 and bethanachol elicited modest increases in cortical periarachnoid cerebrospinal fluid levels of 6-keto-prostaglandin F1 alpha, prostaglandin E2, thromboxane B2 and prostaglandin F2 alpha. Topical acetylcholine (10(-7), 10(-4) M) elicited pial arteriolar constriction and large increases in cerebrospinal fluid prostanoid levels which were blocked by atropine (0.5 mg/kg i.v.) and topical pirenzepine (10(-3) M), but not by topical 4-DAMP. These data demonstrate the existence of M-1 and M-2 receptors in the cerebral circulation of the newborn pig and indicate that acetylcholine elicits cerebrovascular constriction and increased cerebrospinal fluid prostanoid synthesis via activation of M-1 receptors.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1988

The role of prostanoids in the mediation of responses to KC-404, a novel cerebrovasodilator.

The purpose of this study was to characterize the nature of the response to KC-404 in the cerebral microcirculation of the newborn pig. Pial arterioles were observed directly using a closed cranial window in chloralose-anesthetized piglets. Topical application of 100, 300, 1000, 3000 and 10,000 ng/ml of KC-404 produced concentration-dependent increases in pial arteriolar diameter. Diameters were 168 +/- 18, 190 +/- 19 and 238 +/- 21 mu for control, 100 ng/ml and 10,000 ng/ml of KC-404, respectively. Responses to KC-404 (3-isobutyryl-2-isopropylpyrazolo-[1,5a]-pyridine) were blocked by indomethacin (5 mg/kg i.v.). Moreover, KC-404, topically applied to the cerebral cortex, produced small but significant increases in cortical subarachnoid cerebrospinal fluid levels of 6-keto-prostaglandin (PG) F1 alpha and PGE2, whereas thromboxane B2 levels were unchanged. Similar to topical application, i.v. KC-404 (0.5 mg/kg) produced pial arteriolar dilation without significantly altering arterial blood pressure. Intravenous KC-404 also increased cerebrospinal fluid levels of 6-keto-PGF1 alpha and PGE2, whereas thromboxane levels were unchanged. Further, topically applied KC-404 (1 microgram/ml) potentiated dilator responses to PGE2 and PGI2, whereas responses to isoproterenol were unchanged. These data indicate that KC-404 is a potent dilator of cerebral arterioles in newborn pigs. These data also suggest that KC-404 produces cerebral vasodilation predominantly by potentiating prostanoid-mediated dilation.

Animals↗

PubMed1987

Eicosanoid synthesis elicited by norepinephrine in piglet parietal cortex.

We investigated effects of exogenous norepinephrine and isoproterenol on pial arterial diameter and cerebral eicosanoid synthesis in anesthetized newborn pigs. Norepinephrine in artificial cerebrospinal fluid (CSF) constricted pial arteries from 203 +/- 27 micron (X +/- S.E.M.) to 164 +/- 18 micron (20 +/- 2%) (n = 21 vessels from 16 animals) at 10(-4) M. In the same animals, norepinephrine caused the concentration in CSF of 6-keto-prostaglandin F1 alpha to increase from 768 +/- 91 to 1544 +/- 151 pg/ml, thromboxane B2 to increase from 188 +/- 37 to 269 +/- 38 pg/ml, and prostaglandin E2 to increase from 2067 +/- 448 to 6575 +/- 751 pg/ml. Topical application of prostaglandin E2 in CSF to the cortical surface demonstrated that concentrations as low as 10,000 pg/ml were able to dilate pial arteries substantially. Blockade of cyclo-oxygenase activity by indomethacin (5-10 mg/kg, i.v.) potentiated pial arterial constriction to norepinephrine. Topical isoproterenol dilated pial arteries, but isoproterenol did not affect levels of measured eicosanoids in CSF. We conclude that norepinephrine elicits release of prostanoids from the cortical surface, and that these substances limit cerebrovascular constriction to norepinephrine.

Animals↗

PubMed1987

Redistribution of cardiac output after hypothalamic lesions and hemorrhage.

The effects of ablation of the anteroventral portion of the third cerebral ventricle (AV3V) on cardiac output and distribution of regional blood flows were determined in conscious rats using 15 micron radiolabelled microspheres before, and 2 min and 15 min after hemorrhage (n = 11 for each group). Prior to hemorrhage, cerebral blood flow was significantly greater (216 +/- 30 ml/min/100 g), and cerebral vascular resistance was lower (0.60 +/- 0.09 mm Hg/ml/min/100 g) in rats with AV3V lesions than in control-operated animals (132 +/- 16 ml/min/100 g; 0.92 +/- 0.1 mm Hg/ml/min/100 g, respectively), while mean arterial blood pressure, cardiac output, and regional blood flow to other organs were similar. Less blood was withdrawn from animals with AV3V lesions (4.4 +/- 0.6 ml) than from control-operated rats (6.0 +/- 0.5 ml) to reduce blood pressure to approximately 65 mm Hg. Hemorrhage decreased cerebral vascular resistance in control-operated animals (0.52 +/- 0.07 mm Hg/ml/min/100 g), but not in rats with AV3V lesions (0.48 +/- 0.1 mm Hg/ml/min/100 g). Cardiac output and regional blood flow to other organs were similar between rats with AV3V lesions and control-operated animals following hemorrhage. These data demonstrate that electrolytic ablation of the AV3V region results in a selective increase in cerebral blood flow and decreased cerebral vascular resistance, but does not alter the reflex changes in regional blood flow evoked by hemorrhage.

Animals↗

PubMed1987

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.

Animals↗