Increased spontaneous tone in renal arteries of spontaneously hypertensive rats

Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1673-81. doi: 10.1152/ajpheart.00289.2007. Epub 2007 Jun 8.

Abstract

The spontaneous tone of vascular smooth muscle is augmented in hypertension. The present study examined the role of nitric oxide (NO), cyclooxygenase (COX), thromboxane A(2)/prostanoid (TP) and PGE(2)/prostanoid (EP-1) receptors, reactive oxygen species, and large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels in the regulation of spontaneous tone in renal arteries of young and mature Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Rings of arteries, with and without endothelium, were suspended in a myograph for isometric force recording. Spontaneous tone (increase above initial tension) was observed only in arteries of mature SHR and was greater in arteries without endothelium. N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthases) induced larger contractions in arteries of SHR than WKY. Indomethacin (a COX inhibitor), SC-19220 (an EP-1 receptor antagonist), and terutroban (a TP receptor antagonist) reduced the L-NAME-evoked contractions. Tiron (a superoxide anion scavenger), catalase (an enzyme that degrades H(2)O(2)), and deferoxamine (a hydroxyl radical scavenger) augmented the L-NAME-induced contractions in arteries of mature SHR. Charybdotoxin (a BK(Ca) channel blocker) caused contractions in arteries of mature SHR without endothelium and in arteries with endothelium incubated with L-NAME. A decreased protein level of endothelial NO synthase, an increased release of prostacyclin, and an increased expression of EP-1 receptors were observed in arteries of mature SHR. The present study suggests that spontaneous tone is precipitated by age and hypertension. The reduced production of NO, leading to decreased activation of BK(Ca) channels, may leave the actions of endogenous vasoconstrictors unopposed. COX products that activate EP-1 and TP receptors are involved in the development of spontaneous tone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Endothelium, Vascular / physiopathology
  • Hypertension / physiopathology*
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Male
  • Muscle Hypertonia / physiopathology*
  • Nitric Oxide / physiology
  • Potassium Channels / physiology
  • Prostaglandin-Endoperoxide Synthases / physiology
  • Prostaglandins / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Prostaglandin E / physiology
  • Receptors, Prostaglandin E, EP1 Subtype
  • Receptors, Thromboxane A2, Prostaglandin H2 / physiology
  • Renal Artery / physiopathology*

Substances

  • Kcnma1 protein, rat
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Potassium Channels
  • Prostaglandins
  • Ptger1 protein, rat
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP1 Subtype
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Nitric Oxide
  • Prostaglandin-Endoperoxide Synthases