Receptor‐Mediated Events in the Microcirculation

Watts, Stephanie W.; Kanagy, Nancy L.; Lombard, Julian H.

doi:10.1002/cphy.cp020407

Cited by 4 publications

(4 citation statements)

References 648 publications

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“…Many vasoconstrictors act on vascular SMCs through heptihelical receptors coupled to heterotrimeric G q/11 and downstream PLC resulting in hydrolysis of membrane phospholipids, formation of DAG and IP 3 , activation of IP 3 Rs and subsequent release of Ca 2+ that contributes to SMC contraction (1055, 1502) (Fig. 10).…”

Section: Inositol-145-triphosphate Receptorsmentioning

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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Section: Inositol-145-triphosphate Receptorsmentioning

confidence: 99%

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

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

270

347

View full text Add to dashboard Cite

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“…Dopamine in moderate doses stimulates cardiac β -1 adrenoreceptors resulting in a positive inotropic effect and a vasodilation that manifest, itself clinically as an increase in SBP with insignificant change in DBP [35]. This line of reasoning explains our findings of test drug induced clinically relevant vital signs changes starting on days 6-7 of the UPT period onwards (1.5–2 mg/day).…”

Section: Discussionmentioning

confidence: 67%

Dopamine D2R Agonist-Induced Cardiovascular Effects in Healthy Male Subjects: Potential Implications in Clinical Settings

Farha¹,

Baljé-Volkers²,

Tamminga³

et al. 2014

ISRN Neurology

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Dopamine D2 receptor agonists represent a first line treatment option in young patients with signs and symptoms of idiopathic Parkinson's disease. An association between the use of D2 receptor agonists in Parkinson's disease patients and heart failure has been reported. The identification of the underlying mechanism is needed to minimize the resultant cardiovascular morbidity. In a phase I clinical trial, a D2 receptor agonist (pramipexole) was administered to 52 healthy male subjects following a dose escalation scheme. Serial measurements of resting blood pressure, heart rate, and derived parameters including pulse pressure, pulsatile stress, and rate pressure product were analysed. Statistically significant and clinically relevant increases in most of the assessed parameters were found. Ten subjects were removed prematurely from the trial because of clinically significant increases in blood pressure and/or heart rate requiring immediate intervention with IV rescue medications including a selective β-1 blocker. The observed drug-related changes in vital signs were of clinical relevance and might explain some of the cardiovascular morbidity reported in patients receiving D2 receptor agonist in clinical settings. We suggest that the additional use of a β-1 blocking agent might mitigate the risk of cardiovascular morbidity among patients receiving long-term D2 receptor agonists.

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“…The function of other 5-HT receptor subtypes in cremaster arterioles was not examined. Stimulation of vascular 5-HT 1B and 5-HT 2A receptors should result in vasoconstriction, 34 while endothelial cell 5-HT 2B receptors can mediate endothelium-dependent vasodilation. 34 Based on our pharmacologic and genetic evidence, it is unlikely that 5-HT 2B receptors contributed to 5-HT-induced arteriolar vasodilation.…”

Section: Expression Of 5-ht Receptors In Cremaster Microcirculationmentioning

confidence: 99%

“…Stimulation of vascular 5-HT 1B and 5-HT 2A receptors should result in vasoconstriction, 34 while endothelial cell 5-HT 2B receptors can mediate endothelium-dependent vasodilation. 34 Based on our pharmacologic and genetic evidence, it is unlikely that 5-HT 2B receptors contributed to 5-HT-induced arteriolar vasodilation. Inhibition of nitric oxide synthase and endothelium-dependent dilation in wholeanimal studies 12 and studies in rat cremaster muscle 9 failed to affect 5-HT-induced decreases in total peripheral resistance or arteriolar dilation, respectively.…”

Section: Expression Of 5-ht Receptors In Cremaster Microcirculationmentioning

confidence: 99%

5‐HT₇ receptors mediate dilation of rat cremaster muscle arterioles in vivo

et al. 2023

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ObjectiveSerotonin (5‐HT) infusion in vivo causes hypotension and a fall in total peripheral resistance. However, the vascular segment and the receptors that mediate this response remain in question. We hypothesized that 5‐HT7 receptors mediate arteriolar dilation to 5‐HT in skeletal muscle microcirculation.MethodsCremaster muscles of isoflurane‐anesthetized male Sprague‐Dawley rats were prepared for in vivo microscopy of third‐ and fourth‐order arterioles and superfused with physiological salt solution at 34°C. Quantitative real‐time PCR (RT‐PCR) was applied to pooled samples of first‐ to third‐order cremaster arterioles (2–4 rats/sample) to evaluate 5‐HT7 receptor expression.ResultsTopical 5‐HT (1–10 nmols) or the 5‐HT1/7 receptor agonist, 5‐carboxamidotryptamine (10–30 nM), dilated third‐ and fourth‐order arterioles, responses that were abolished by 1 μM SB269970, a selective 5‐HT7 receptor antagonist. In contrast, dilation induced by the muscarinic agonist, methacholine (100 nmols) was not inhibited by SB269970. Serotonin (10 nmols) failed to dilate cremaster arterioles in 5‐HT7 receptor knockout rats whereas arterioles in wild‐type litter mates dilated to 1 nmol 5‐HT, a response blocked by 1 μM SB269970. Quantitative RT‐PCR revealed that cremaster arterioles expressed mRNA for 5‐HT7 receptors.Conclusions5‐HT7 receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5‐HT‐induced hypotension, in vivo.

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Receptor‐Mediated Events in the Microcirculation

Cited by 4 publications

References 648 publications

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

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

Dopamine D2R Agonist-Induced Cardiovascular Effects in Healthy Male Subjects: Potential Implications in Clinical Settings

5‐HT₇ receptors mediate dilation of rat cremaster muscle arterioles in vivo

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Receptor‐Mediated Events in the Microcirculation

Cited by 4 publications

References 648 publications

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

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

Dopamine D2R Agonist-Induced Cardiovascular Effects in Healthy Male Subjects: Potential Implications in Clinical Settings

5‐HT7 receptors mediate dilation of rat cremaster muscle arterioles in vivo

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5‐HT₇ receptors mediate dilation of rat cremaster muscle arterioles in vivo