Renal vascular reactivity to P(2)-purinoceptor activation in spontaneously hypertensive rats

Pharmacology. 2000 Jan;60(1):47-50. doi: 10.1159/000028346.

Abstract

This study was performed to determine the possible contribution of an imbalance between P(2X) (vasoconstriction) and P(2Y) (vasodilation)-purinergic reactivity to the increased vascular resistance of spontaneously hypertensive rats (SHR). The vasoactive responses to alpha,beta-methylene ATP and 2-methylthio ATP specific agonists, respectively, for P(2X) and P(2Y) purinergic receptors were characterized in isolated perfused kidneys from Wistar Kyoto (WKY) and SHR. To analyze P(2X)- and P(2Y)-purinergic reactivity we used phenylephrine and barium chloride, or acethylcholine (ACh) and sodium nitroprusside (NP) as reference compounds, respectively. The renal vasculature from SHR showed markedly enhanced reactivity to alpha,beta-methylene ATP, phenylephrine and barium chloride. The dose-response curves were characterized by a similar threshold, with a greater maximal response. There were no significant differences in the dose-response curves or in maximal vasodilation to 2-methylthio ATP, ACh or NP when both groups were compared, except at the dose of 10(-6) g/g kidney weight of NP in which the SHR group showed an increased responsiveness. The results indicate that the increased responsiveness of kidneys from SHR to alpha,beta-methylene ATP may be due to nonspecific functional changes in the renal vasculature rather than to a specific alteration in the activity of renal P(2X)-purinoceptors. Our results also indicate that P(2Y)-purinergic reactivity, nitric oxide-induced vasodilation and the cGMP-dependent mechanisms of vasodilation are well preserved in SHR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • In Vitro Techniques
  • Kidney / blood supply
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • Perfusion
  • Purinergic P2 Receptor Agonists
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Purinergic P2 / metabolism*
  • Thionucleotides / pharmacology
  • Vascular Resistance
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects

Substances

  • Purinergic P2 Receptor Agonists
  • Receptors, Purinergic P2
  • Thionucleotides
  • Adenosine Triphosphate
  • alpha,beta-methyleneadenosine 5'-triphosphate
  • 2-methylthio-ATP