Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regional cerebral blood flow (rCBF) during controlled hemorrhagic hypotension (140-20 mm Hg) was assessed 10-14 days after chronic unilateral sectioning of parasympathetic and/or sensory fibers innervating pial vessels in spontaneously hypertensive rats (SHR). rCBF was measured in the cortical barrel fields bilaterally by laser Doppler blood flowmetry. Immunohistochemistry of middle cerebral artery (MCA) whole mount preparations was used to verify the surgical lesion. During hemorrhagic hypotension, rCBF was equivalent on the two sides in shams, after selective sensory denervation, or in parasympathetically sectioned animals exhibiting small decreases (less than or equal to 30%) in immunoreactive vasoactive intestinal peptide (VIP)-containing fibers. After chronic parasympathetic denervation, decreases in perfusion pressure were accompanied by greater reductions in rCBF on the lesioned side; changes in vascular resistance were also attenuated on that side. The rCBF response to hypercapnia (PaCO2 50 mm Hg), however, was symmetrical and robust. To examine the effects of impaired neurogenic vasodilation on the pathophysiology of cerebral ischemia, infarct size was measured 24 h following tandem MCA occlusion in denervated animals. Infarction volume was larger after selective parasympathetic sectioning (sham, 156 +/- 27 vs. 196 +/- 32 mm3, respectively) but only in those denervated animals demonstrating greater than or equal to 40% decrease in immunoreactive VIP-containing fibers within the ipsilateral MCA. Lower than expected blood flow/perfusion pressure in the cortex distal to an occluded blood vessel may relate the observed blood flow responses to the occurrence of larger cortical infarcts in parasympathetically denervated animals. If true, the findings suggest a novel role for neurogenic vasodilation in the pathophysiology of cerebral ischemia and in rCBF regulation within the periinfarction zone.
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PMID:Chronic parasympathetic sectioning decreases regional cerebral blood flow during hemorrhagic hypotension and increases infarct size after middle cerebral artery occlusion in spontaneously hypertensive rats. 161 40

Animal studies suggest that the neuropeptides, substance P and vasoactive intestinal peptide (VIP), may influence carotid body chemoreceptor activity and that substance P may take part in the carotid body response to hypoxia. The effects of these peptides on resting ventilation and on ventilatory responses to hypoxia and to hypercapnia have been investigated in six normal humans. Infusions of substance P (1 pmol.kg-1.min-1) and of VIP (6 pmol.kg-1.min-1) were compared with placebo and with nitroprusside (5 micrograms.kg-1.min-1) as a control for the hypotensive action of the peptides. Both peptides caused significantly less hypotension than nitroprusside. Substance P and nitroprusside caused significantly greater increases in ventilation and in the hypoxic ventilatory response than VIP. No changes were seen in hypercapnic sensitivity. The stimulation of ventilation and the differential effects on ventilatory chemosensitivity that accompanied hypotension are consistent either with stimulation of carotid body chemoreceptor activity or with an interaction with peripheral chemoreceptor input to the respiratory center, as is seen in animals. The similar cardiovascular but different ventilatory effects of the peptides suggest that substance P may also stimulate the carotid body in a manner independent of the effect of hypotension. This is consistent with a role of substance P in the hypoxic ventilatory response in humans.
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PMID:Ventilatory effects of substance P, vasoactive intestinal peptide, and nitroprusside in humans. 169 Feb 2

In chloralose-urethanized cats, vasoactive intestinal peptide (VIP), applied by superfusion in steady-state concentration (10(-10)-10(-6) M) onto cortical vessels in situ resulted in a rapid concentration-dependent vasodilatation in vessels that were mildly constricted by prostaglandin F2 alpha (PGF2 alpha) (5 X 10(-5) M) or hypocarbia (PaCO2 = 26). The maximum dilatation produced by VIP (10(-6) M) was about 60% over baseline in pial arteries and 40% in pial veins. Blockade of local neuronal activity with tetrodotoxin (TTX) (10(-5) M) had no effect on the VIP-evoked dilation of pial vessels. Activation of the cortex by either direct electrical stimulation or indirectly by stimulation of the mesencephalic reticular formation (MRF) resulted in a rapid dilatation of pial arterioles and venules. The vasodilatory effects of VIP and of cortical activation via direct cortical stimulation were not blocked by phentolamine (10(-4) M), propranolol (10(-4) M), atropine (10(-4) M), or naloxone (10(-4) M), indicating that the stimulated vasodilatation was not mediated by adrenergic, cholinergic, or opiate receptors. The dilatory effects of MRF, but not direct cortical stimulation, were not blocked by TTX. VIP antiserum (1:25) preincubated in cortical cups had no effect on resting vessel diameter, but resulted in a significant, though subtotal, reduction in the vasodilatation elicited by direct cortical and MRF stimulation. Normal rabbit sera or VIP antiserum preincubated with saturating amounts of VIP were ineffective. In similar experiments, pial arteriolar and venular dilation evoked by hypercarbia was not attenuated by cortically applied VIP antisera. These observations suggest that pial dilation evoked by local increases in neuronal activity may be mediated in part by the local release of VIP from intrinsic neurons. Such a substrate would define a close obligatory coupling between local neuronal activation and local perfusion, such that nutritive flow could be enhanced prior to the onset of any metabolic deficit.
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PMID:Cortical vasodilatation produced by vasoactive intestinal polypeptide (VIP) and by physiological stimuli in the cat. 310 70

The most abundant prostaglandin produced by brain tissue varies from species to species. The most abundant prostaglandin produced by brain microvessels is PGI2, PGG2, PGH2, PGI2, PGE2, PGD2, and arachidonic acid dilated cerebral arterioles. Cyclooxygenase inhibitors (indomethacin, AHR-5850), in doses that reduced prostaglandin synthesis substantially, did not affect resting vascular caliber and did not influence the responses of cerebral arterioles to arterial hypoxia, arterial hypercapnia, or arterial hypocapnia, suggesting that prostaglandins are not involved in the mediation of these responses. The vasodilator action of vasoactive intestinal peptide on cerebral arterioles was blocked by these cyclooxygenase inhibitors. The cerebral arteriolar damage induced by fluid-percussion brain injury was inhibited by pretreatment with cyclooxygenase inhibitors, or with free radical scavengers. Topical application of arachidonic acid or PGG2, reproduced the damage seen with brain injury. These findings show that prostaglandins are mediators of the cerebral arteriolar damage due to brain injury and that their mechanism of action is dependent on the generation of free oxygen radicals.
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PMID:Prostaglandins in physiological and in certain pathological responses of the cerebral circulation. 723 14

Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective in numerous models. Impairment of cerebrovascular reactivity (CR) contributes to ischemia/reperfusion (I/R)-induced neuronal damage. We tested whether PACAP and/or VIP preserve CR to I/R-sensitive dilator responses dependent on endothelial and/or neuronal function. Accordingly, changes in pial arteriolar diameters in response to hypercapnia (5-10% CO(2) ventilation) or topical N-methyl-d-aspartate (NMDA, 10(-4) M) were determined before and after I/R via intravital microscopy in anesthetized/ventilated piglets. Local pretreatment with non-vasoactive doses of PACAP (10(-8) M) and VIP (10(-9) M) prevented the attenuation of postischemic CR to hypercapnia; to 10% CO(2), the CR values were 27+/-8% vs 92+/-5% vs 88+/-13% (vehicle vs PACAP38 vs VIP, CR expressed as a percentage of the response before I/R, mean+/-SEM, n=8-8, p<0.05). PACAP, but not VIP, preserved CR to NMDA after I/R, with CR values of 31+/-10% vs 87+/-8% vs 35+/-12% (vehicle vs PACAP38 vs VIP, n=6-6). Unlike PACAP, VIP-induced vasodilation has not yet been investigated in the piglet. We tested whether VIP-induced arteriolar dilation was sensitive to inhibitors of cyclooxygenase (COX)-1 (SC-560, 1 mg/kg), COX-2 (NS-398, 1 mg/kg), indomethacin (5 mg/kg), and nitric oxide synthase (L-NAME, 15 mg/kg). VIP (10(-8)-10(-7)-10(-6) M, n=8) induced reproducible, dose-dependent vasodilation of 16+/-3%, 33+/-6%, and 70+/-8%. The response was unaffected by all drugs, except that the vasodilation to 10(-8) M VIP was abolished by SC-560 and indomethacin. In conclusion, PACAP and VIP differentially preserve postischemic CR; independent of their vasodilatory effect.
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PMID:PACAP and VIP differentially preserve neurovascular reactivity after global cerebral ischemia in newborn pigs. 1953 45