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Molecular and functional characterization of Kv 7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats.

Jepps, TA; Olesen, SP; Greenwood, IA; Dalsgaard, T (2016) Molecular and functional characterization of Kv 7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats. British Journal of Pharmacology, 173 (9). pp. 1478-1490. ISSN 1476-5381 https://doi.org/10.1111/bph.13444
SGUL Authors: Greenwood, Iain Andrew

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Abstract

BACKGROUND AND PURPOSE: KCNQ-encoded voltage-dependent potassium channels (Kv 7) are involved in the regulation of vascular tone. In this study we evaluated the influence of Kv 7 channel activation on smooth muscle relaxation in rat penile arteries and corpus cavernosum from normal and spontaneously hypertensive, heart failure-prone (SHHF) rats - a rat model of human metabolic syndrome. EXPERIMENTAL APPROACH: Quantitative PCR and immunohistochemistry were used to determine the expression of KCNQ isoforms in penile tissue. Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from normal and SHHF rats. KEY RESULTS: Transcripts for KCNQ3, KCNQ4 and KCNQ5 were detected in penile arteries and corpus cavernosum. KCNQ1 was only found in corpus cavernosum. Immunofluorescence signals to Kv 7.4 and Kv 7.5 were found in penile arteries, penile veins and corpus cavernosum. The Kv 7.2-7.5 activators, ML213 and BMS204352, relaxed pre-contracted penile arteries and corpus cavernosum independently of nitric oxide synthase or endothelium-derived hyperpolarization. Relaxations to sildenafil, a PDE5 inhibitor, and sodium nitroprusside (SNP), an nitric oxide donor, were reduced by blocking Kv 7 channels with linopirdine in penile arteries and corpus cavernosum. In SHHF rat penile arteries and corpus cavernosum, relaxations to ML213 and BMS204352 were attenuated, and the blocking effect of linopirdine on sildenafil-induced and SNP-induced relaxations reduced. KCNQ3, KCNQ4 and KCNQ5 were down-regulated, and KCNQ1 was up-regulated in corpus cavernosum from SHHF rats. KCNQ1-5 transcripts remained unchanged in penile arteries from SHHF rats. CONCLUSIONS AND IMPLICATIONS: These data suggest that Kv 7 channels play a role in erectile function and contribute to the pathophysiology of erectile dysfunction, an early indicator of cardiovascular disease.

Item Type: Article
Additional Information: © 2016 The British Pharmacological Society
Keywords: Pharmacology & Pharmacy, 1115 Pharmacology And Pharmaceutical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: British Journal of Pharmacology
ISSN: 1476-5381
Language: eng
Dates:
DateEvent
26 February 2016Published
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
608765Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
107118Novo Nordisk UK Research Foundationhttp://dx.doi.org/10.13039/501100000329
MR/K019074/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PG/12/63/29824British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
PubMed ID: 26802314
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107682
Publisher's version: https://doi.org/10.1111/bph.13444

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