Contributions of K<sub>ATP</sub>
 and K<sub>Ca</sub>
 channels to cerebral arteriolar dilation to hypercapnia in neonatal brain

Nnorom, Chukwuma C.; Davis, Corinne A.; Fedinec, Alexander L.; Howell, Khadesia; Jaggar, Jonathan H.; Parfenova, Helena; Pourcyrous, Massroor; Leffler, Charles W.

doi:10.14814/phy2.12127

Cited by 12 publications

(19 citation statements)

References 22 publications

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“…Newborn pigs at 1-5 days old and weighing 1.5-3.5 kg were used (n ϭ 50). Pigs were anesthetized with ketamine (33 mg/kg im) and acepromazine (3.3 mg/kg im), intubated via tracheostomies, and placed on mechanical ventilation to maintain blood gases at the normal range for newborn piglets (arterial PCO 2: 30 -40 mmHg, arterial PO2: 70 -90 mmHg, and pH 7.3-7.4), as previously described (12,13,22). Femoral artery catheterization was performed for continuous blood pressure monitoring and arterial blood gas sampling.…”

Section: Methodsmentioning

confidence: 99%

“…SNP and isoproterenol were dissolved in distilled water and diluted to 10 Ϫ6 M with aCSF. The concentrations of the K ϩ channel blockers glibenclamide and paxilline were selected on the basis of our previous publications (12,16,17,22). Glibenclamide stock solution in DMSO was diluted with aCSF to 10 Ϫ7 M. Paxilline stock solution in ethanol was diluted with aCSF to 4 ϫ 10 Ϫ5 M. DL-propargylglycine (PPG), a selective inhibitor of CSE-catalyzed H2S formation, was dissolved in water and diluted to 5 mM with aCSF.…”

Section: Methodsmentioning

confidence: 99%

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H₂S mediates the vasodilator effect of endothelin-1 in the cerebral circulation

Patel

Fedinec

Liu

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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H2S is an endogenous gasotransmitter that increases cerebral blood flow. In the cerebral vascular endothelium, H2S is produced by cystathionine δ-lyase (CSE). Endothelin-1 (ET-1) has constrictor and dilator influences on the cerebral circulation. The mechanism of the vasodilation caused by ET-1 may involve endothelium-derived factors. We hypothesize that ET-1-elicited dilation of pial arterioles requires an elevation of H2S production in the cerebral vascular endothelium. We investigated the effects of ET-1 on CSE-catalyzed brain H2S production and pial arteriolar diameter using cranial windows in newborn pigs in vivo. H2S was measured in periarachnoid cerebrospinal fluid. ET-1 (10−12–10−8 M) caused an elevation of H2S that was reduced by the CSE inhibitors propargylglycine (PPG) and β-cyano-l-alanine (BCA). Low doses of ET-1 (10−12–10−11 M) produced vasodilation of pial arterioles that was blocked PPG and BCA, suggesting the importance of H2S influences. The vasodilator effects of H2S may require activation of smooth muscle cell membrane ATP-sensitive K+ (KATP) channels and large-conductance Ca2+-activated K+ (BK) channels. The KATP inhibitor glibenclamide and the BK inhibitor paxilline blocked CSE/H2S-dependent dilation of pial arterioles to ET-1. In contrast, the vasoconstrictor response of pial arterioles to 10−8 M ET-1 was not modulated by PPG, BCA, glibenclamide, or paxilline and, therefore, was independent of CSE/H2S influences. Pial arteriolar constriction response to higher levels of ET-1 was independent of CSE/H2S and KATP/BKCa channel activation. These data suggest that H2S is an endothelium-derived factor that mediates the vasodilator effects of ET-1 in the cerebral circulation via a mechanism that involves activation of KATP and BK channels in vascular smooth muscle. NEW & NOTEWORTHY Disorders of the cerebral circulation in newborn infants may lead to lifelong neurological disabilities. We report that vasoactive peptide endothelin-1 exhibits vasodilator properties in the neonatal cerebral circulation by stimulating production of H2S, an endothelium-derived messenger with vasodilator properties. The ability of endothelin-1 to stimulate brain production of H2S may counteract the reduction in cerebral blood flow and prevent the cerebral vascular dysfunction caused by stroke, asphyxia, cerebral hypoxia, ischemia, and vasospasm.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

H₂S mediates the vasodilator effect of endothelin-1 in the cerebral circulation

Patel

Fedinec

Liu

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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“…K ATP channels do not appear to be active in the cerebral circulation under resting conditions in a variety of model systems [see (402) for numerous references and (618, 838, 877, 1096, 1422, 1510)].…”

Section: Katp Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

270

347

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Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

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“…Indeed, decreases in the reactivity of the cerebral vasculature to CO 2 may be a useful predictor of stroke risk [29 && ]. These mediators then activate K-ATP and K-Ca channels through intracellular second messengers (cGMP/cAMP) resulting in decreased intracellular-Ca 2þ and vasodilation [31]. Mechanisms leading to cerebral vasodilatation or relaxation differ between adults and neonates.…”

Section: Key Pointsmentioning

confidence: 99%