Effect of amiloride analogs on DOCA-salt-induced hypertension in rats

Am J Physiol. 1999 Jun;276(6):H2215-20. doi: 10.1152/ajpheart.1999.276.6.H2215.

Abstract

Intracerebroventricular infusions of an amiloride analog, benzamil, reduce blood pressure in several rat models of hypertension. This effect has been attributed to an inhibition of amiloride-sensitive Na+ channels in the brain. This study examines whether intracerebroventricular benzamil would prevent the onset of deoxycorticosterone acetate (DOCA)-salt-induced hypertension in rats and whether this effect correlates with an inhibition of ion transport through the known amiloride-sensitive cation channels at the blood-brain barrier. We also examine whether the effects of benzamil on blood pressure are mediated by a Na+ channel by comparing the effects of different amiloride analogs. Benzamil (0.15 and 0.5 microgram/h icv) did significantly attenuate the increase in blood pressure induced by DOCA treatment. This antihypertensive effect, however, was not associated with an alteration in a blood-brain barrier ion transport as assessed by measurements of blood-to-brain 22Na transport and cerebral spinal fluid Na+ and K+ concentrations. Indeed, intracerebroventricular infusion of dimethyl amiloride, an amiloride analog with low affinity for Na+ channels, also attenuated the increase in blood pressure induced by DOCA-salt treatment. Comparisons of the effects of benzamil, dimethyl amiloride, and 3,4-dichlorobenzamil, another amiloride analog, suggest that these antihypertensive effects are mediated by an inhibition of Na+/Ca2+ exchange in the brain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amiloride / analogs & derivatives*
  • Amiloride / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Desoxycorticosterone*
  • Hypertension / chemically induced*
  • Hypertension / physiopathology*
  • Injections, Intraventricular
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Chloride*

Substances

  • benzamil
  • 3',4'-dichlorobenzamil
  • 5-dimethylamiloride
  • Desoxycorticosterone
  • Sodium Chloride
  • Amiloride