Effects of hydralazine on contractile responses to alpha 1 and alpha 2-adrenoceptor agonists in isolated rubbed rat aorta

Gen Pharmacol. 1994 Jan;25(1):165-72. doi: 10.1016/0306-3623(94)90028-0.

Abstract

1. Effects of hydralazine on contractile responses to noradrenaline (an alpha 1- and alpha 2-adrenoceptor agonist) to phenylephrine and methoxamine (both selective alpha 1-adrenoceptor agonists) and to clonidine and BHT-920 (both relatively selective alpha 2-adrenoceptor agonists) were examined in isolated rat aorta deprived of endothelium. Hydralazine (1 mM) produced a rightward shift with depression of the maximal tension of the concentration-response curves for all the agonists tested. The effects on curves for clonidine and BHT-920 (partial agonists) were greater than on curves for noradrenaline, phenylephrine and methoxamine (full agonists). 2. The inhibitory effect of prazosin (pA2, about 10) was much greater than that of yohimbine (pA2, about 7) for all the agonists. 3. In tissues pretreated with phenoxybenzamine, hydralazine (1 mM) inhibited the residual response to all the agonists. The inhibitory effect on residual response to full agonists was similar to that observed on response to partial agonists in tissues not treated with phenoxybenzamine. 4. The relationship between maximal response and percentage receptor occupancy was nonlinear for full agonists, but near-linear for partial agonists. 5. These results indicate that the responses induced by noradrenaline, phenylephrine, methoxamine, clonidine and BHT-920 in the rat aorta are due to the activation of alpha 1-adrenoceptors and confirm the vasorelaxant action of hydralazine. 6. These results also suggest that the differential effects of hydralazine on the responses to alpha-adrenoceptor agonists may be due to differences in the amount of receptor reserve available available in this blood vessel for full agonists (noradrenaline, phenylephrine or methoxamine) and partial agonists (clonidine or BHT-920).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Drug Interactions
  • Endothelium, Vascular / physiology
  • Female
  • Hydralazine / pharmacology*
  • In Vitro Techniques
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / drug effects*
  • Receptors, Adrenergic, alpha-1 / physiology
  • Receptors, Adrenergic, alpha-2 / drug effects*
  • Receptors, Adrenergic, alpha-2 / physiology

Substances

  • Adrenergic alpha-Agonists
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Hydralazine