Altered KATP Channel Subunits Expression and Vascular Reactivity in Spontaneously Hypertensive Rats With Age

J Cardiovasc Pharmacol. 2016 Aug;68(2):143-9. doi: 10.1097/FJC.0000000000000394.

Abstract

ATP-sensitive potassium (KATP) channels link membrane excitability to metabolic state to regulate a series of biological activities including the vascular tone. However, their ability to influence hypertension is controversial. Here we aim to investigate possible alteration of KATP channel in vascular smooth muscles (VSMs) during hypertension development process. In this study, we used 16-week-old spontaneously hypertensive rats (SHRs), 49-week-old SHRs, and their age-matched Wistar-Kyoto rats to study the expression of VSM KATP subunits at the mRNA and protein level and the function of VSM KATP by observing the relaxation reactivity of isolated aorta rings to KATP modulators. We found that the expression of VSM KATP subunits Kir6.1 and sulfonylurea receptor (SUR2B) decreased during hypertension. Moreover, the expression of SUR2B and Kir6.1 in 49-week-old SHRs decreased much more than that in 16-week-old SHRs. Furthermore, the aorta rings of 49-week-old SHRs showed lower reactivity to diazoxide than 16-week-old SHRs. This study suggests that KATP channels in VSM subunits Kir6.1 and SUR2B contribute to modify the functionality of this channel in hypertension with age.

Publication types

  • Comparative Study

MeSH terms

  • Age Factors
  • Aging / metabolism*
  • Animals
  • Aorta / metabolism
  • Aorta / physiopathology
  • Blood Pressure* / drug effects
  • Diazoxide / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Hypertension / drug therapy
  • Hypertension / genetics
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • KATP Channels / genetics
  • KATP Channels / metabolism*
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / physiopathology
  • Potassium Channel Blockers / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sulfonylurea Receptors / genetics
  • Sulfonylurea Receptors / metabolism*
  • Vasodilation* / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Abcc9 protein, rat
  • KATP Channels
  • Potassium Channel Blockers
  • RNA, Messenger
  • Sulfonylurea Receptors
  • Vasodilator Agents
  • uK-ATP-1 potassium channel
  • Diazoxide