Altered vascular responsiveness to Kv7 channel activators in old normotensive and hypertensive rats

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC266

Poster Communications: Altered vascular responsiveness to Kv7 channel activators in old normotensive and hypertensive rats

J. Stott1, V. Barrese1, I. A. Greenwood1

1. St George's University of London, London, United Kingdom.

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The Kv7 family of voltage gated potassium channels contribute to the maintenance of vascular tone, a function which is impaired in hypertension. There are three Kv7 isoforms consistently expressed in the vasculature – Kv7.1, 7.4 and 7.5 – but it is the reduction in Kv7.4 function and expression that has been attributed to compromised vascular function. Aging is a prime risk factor for the development of cardiovascular disease, but the status of Kv7 channels in the aging vasculature is not clear. Using male Wistar normotensive (NT) and hypertensive (SHR) rats at 3 and 12 months of age, we investigated the vasorelaxant responses to the Kv7 activators ML213 (Kv7.4 activator) and RL-3 (Kv7.1 activator) on segments of mesenteric and renal arteries (MA and RA, respectively) by isometric tension recording in order to determine any functional change in Kv7 responses with aging. Experiments were performed in accordance with the UK Animal (Scientific Procedures) Act 1986, all data are presented as mean±SEM. ML213 relaxations in both MA and RA of 12 month SHR were reduced compared to 12 month NT animals (from 53.9±11.9 to 92.9±6.8% at 300nM in MA (n=4-5, p<0.01) and from 47.5±9.4 to 91±4.1 % relaxation at 10μM in RA (n=5, p<0.005 determined by 2-way ANOVA)). Relaxations to RL-3 were also compromised in 12 month SHR compared with 12 month NT (from 63.5±9.8 to 99.7±0.7 % relaxation at 100nM in MA (n=3-4, p<0.01) and from 64.4±16.4 to 92.7±5.6 % relaxation at 10μM in RA (n=5, p< 0.01 determined by 2-way ANOVA)). With aging, 12 month NT animals showed impaired relaxations to ML213 in the RA compared to their 3 month counterparts (from 16.8±11.6 to 96.1±3.6% relaxation at 300nM (n=4-5, p<0.005)) whilst relaxations to RL-3 were also reduced (from 36±11.1 to 92.7±3.6 % at 3μM (n=5, p<0.005 determined by 2-way ANOVA)). In contrast, the mesenteric arteries of 12 month NT showed no significant difference in relaxations to ML213 compared to 3 month animals. These findings reveal that the functional role of Kv7 channels is altered in the vasculature with aging and impaired in 12 month SHR compared with NT animals. This data shows for the first time the changing contribution of Kv7 channels to vascular reactivity with age, which could have profound implications for our understanding of disease pathogenesis and the development of hypertension.



Where applicable, experiments conform with Society ethical requirements.

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