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Reduced activity of SKC a and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats.

Kong BW, Man RY, Gao Y, Vanhoutte PM, Leung SW - Pharmacol Res Perspect (2015)

Bottom Line: EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging.Pharmacological experiments suggested a reduced involvement of SKC a and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR.These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR, China.

ABSTRACT
Aging is accompanied by endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) and/or reduced endothelium-dependent hyperpolarizations (EDH). This study examines the hypothesis that hypertension aggravates the impairment of EDH-type relaxation due to aging. EDH-type relaxations were studied in superior mesenteric arteries isolated from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats of 12, 36, 60, and 72 weeks of age. EDH-type relaxations in WKY were reduced with aging, and this was associated with an impairment of the function of small-conductance calcium-activated potassium channels (SKC a) and sodium-potassium ATPase (Na-K ATPase). EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging. Pharmacological experiments suggested a reduced involvement of SKC a and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR. These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension. The latter exacerbation appears to involve proteins associated with the process of cellular senescence and is related to impaired function of SKC a and Na-K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats.

No MeSH data available.


Related in: MedlinePlus

Acetylcholine-induced relaxations of superior mesenteric arteries of (Upper) WKY and (Lower) SHR at various ages in the presence of (Left) indomethacin (cyclooxygenase inhibitor; 10−5 mol/L) or (Right) indomethacin (10−5 mol/L) alone, TRAM-34 (IKCa inhibitor; 5 × 10−7 mol/L) and UCL 1684 (SKCa inhibitor; 5 × 10−7 mol/L). Values are means ± SEM of six to eight experiments. *P < 0.05 compared with corresponding 12-week-old groups.
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fig02: Acetylcholine-induced relaxations of superior mesenteric arteries of (Upper) WKY and (Lower) SHR at various ages in the presence of (Left) indomethacin (cyclooxygenase inhibitor; 10−5 mol/L) or (Right) indomethacin (10−5 mol/L) alone, TRAM-34 (IKCa inhibitor; 5 × 10−7 mol/L) and UCL 1684 (SKCa inhibitor; 5 × 10−7 mol/L). Values are means ± SEM of six to eight experiments. *P < 0.05 compared with corresponding 12-week-old groups.

Mentions: In mesenteric arteries isolated from WKY, acetylcholine-induced relaxations in the presence of indomethacin (10−5 M) alone (Fig.2, Upper Left) or in that of the combination of TRAM-34 [IKCa channel blocker, 5 × 10−7 M (Zou et al. 2010)] plus UCL 1684 [SKCa channel blocker, 5 × 10−7 M (Zou et al. 2010)] were similar among the different age groups (Fig.2, Upper Right). However, in SHR arteries, acetylcholine-induced relaxations in the presence of indomethacin decreased with aging (Fig.2, Lower Left). In the presence of indomethacin, TRAM-34 and UCL 1684, full relaxation in response to acetylcholine was observed in arteries of 12-week-old SHR, and this relaxation was reduced in 60- and 72-weeks-old SHR (Fig.2, Lower Right).


Reduced activity of SKC a and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats.

Kong BW, Man RY, Gao Y, Vanhoutte PM, Leung SW - Pharmacol Res Perspect (2015)

Acetylcholine-induced relaxations of superior mesenteric arteries of (Upper) WKY and (Lower) SHR at various ages in the presence of (Left) indomethacin (cyclooxygenase inhibitor; 10−5 mol/L) or (Right) indomethacin (10−5 mol/L) alone, TRAM-34 (IKCa inhibitor; 5 × 10−7 mol/L) and UCL 1684 (SKCa inhibitor; 5 × 10−7 mol/L). Values are means ± SEM of six to eight experiments. *P < 0.05 compared with corresponding 12-week-old groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492766&req=5

fig02: Acetylcholine-induced relaxations of superior mesenteric arteries of (Upper) WKY and (Lower) SHR at various ages in the presence of (Left) indomethacin (cyclooxygenase inhibitor; 10−5 mol/L) or (Right) indomethacin (10−5 mol/L) alone, TRAM-34 (IKCa inhibitor; 5 × 10−7 mol/L) and UCL 1684 (SKCa inhibitor; 5 × 10−7 mol/L). Values are means ± SEM of six to eight experiments. *P < 0.05 compared with corresponding 12-week-old groups.
Mentions: In mesenteric arteries isolated from WKY, acetylcholine-induced relaxations in the presence of indomethacin (10−5 M) alone (Fig.2, Upper Left) or in that of the combination of TRAM-34 [IKCa channel blocker, 5 × 10−7 M (Zou et al. 2010)] plus UCL 1684 [SKCa channel blocker, 5 × 10−7 M (Zou et al. 2010)] were similar among the different age groups (Fig.2, Upper Right). However, in SHR arteries, acetylcholine-induced relaxations in the presence of indomethacin decreased with aging (Fig.2, Lower Left). In the presence of indomethacin, TRAM-34 and UCL 1684, full relaxation in response to acetylcholine was observed in arteries of 12-week-old SHR, and this relaxation was reduced in 60- and 72-weeks-old SHR (Fig.2, Lower Right).

Bottom Line: EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging.Pharmacological experiments suggested a reduced involvement of SKC a and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR.These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR, China.

ABSTRACT
Aging is accompanied by endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) and/or reduced endothelium-dependent hyperpolarizations (EDH). This study examines the hypothesis that hypertension aggravates the impairment of EDH-type relaxation due to aging. EDH-type relaxations were studied in superior mesenteric arteries isolated from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats of 12, 36, 60, and 72 weeks of age. EDH-type relaxations in WKY were reduced with aging, and this was associated with an impairment of the function of small-conductance calcium-activated potassium channels (SKC a) and sodium-potassium ATPase (Na-K ATPase). EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging. Pharmacological experiments suggested a reduced involvement of SKC a and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR. These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension. The latter exacerbation appears to involve proteins associated with the process of cellular senescence and is related to impaired function of SKC a and Na-K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats.

No MeSH data available.


Related in: MedlinePlus