JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Add like
Add dislike
Add to saved papers

KMUP-1 ameliorates monocrotaline-induced pulmonary arterial hypertension through the modulation of Ca2+ sensitization and K+-channel.

Life Sciences 2010 May 9
AIMS: This study investigates the actions of KMUP-1 on RhoA/Rho-kinase (ROCK)-dependent Ca(2+) sensitization and the K(+)-channel in chronic pulmonary arterial hypertension (PAH) rats.

MAIN METHODS: Sprague-Dawley rats were divided into control, monocrotaline (MCT), and MCT+KMUP-1 groups. PAH was induced by a single intraperitoneal injection (i.p.) of MCT (60 mg/kg). KMUP-1 (5 mg/kg, i.p.) was administered once daily for 21 days to prevent MCT-induced PAH. All rats were sacrificed on day 22.

KEY FINDINGS: MCT-induced increased right ventricular systolic pressure (RVSP) and right ventricular hypertrophy were prevented by KMUP-1. In myograph experiments, KCl (80 mM), phenylephrine (10 microM) and K(+) channel inhibitors (TEA, 10 mM; paxilline, 10 microM; 4-AP, 5 mM) induced weak PA contractions in MCT-treated rats compared to controls, but the PA reactivity was restored in MCT+KMUP-1-treated rats. By contrast, in beta-escin- or alpha-toxin-permeabilized PAs, CaCl(2)-induced (1.25 mM, pCa 5.1) contractions were stronger in MCT-treated rats, and this action was suppressed in MCT+KMUP-1-treated rats. PA relaxation in response to the ROCK inhibitor Y27632 (0.1 microM) was much higher in MCT-treated rats than in control rats. In Western blot analysis, the expression of Ca(2+)-activated K(+) (BK(Ca)) and voltage-gated K(+) channels (Kv2.1 and Kv1.5), and ROCK II proteins was elevated in MCT-treated rats and suppressed in MCT+KMUP-1-treated rats. We suggest that MCT-treated rats upregulate K(+)-channel proteins to adapt to chronic PAH.

SIGNIFICANCE: KMUP-1 protects against PAH and restores PA vessel tone in MCT-treated rats, attributed to alteration of Ca(2+) sensitivity and K(+)-channel function.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app