Functional subtypes of renal alpha1-adrenoceptor in diabetic and non-diabetic 2K1C Goldblatt renovascular hypertension

Acta Pharmacol Sin. 2008 May;29(5):564-72. doi: 10.1111/j.1745-7254.2008.00788.x.

Abstract

Aim: This study investigates the subtypes of the alpha1-adrenoceptor mediating the adrenergically-induced renal vasoconstrictor responses in streptozotocin-induced diabetic and non-diabetic 2-kidney one clip (2K1C) Goldblatt hypertensive rats.

Methods: The renal blood flow responses to renal nerve stimulation, noradrenaline, phenylephrine, and methoxamine were measured in the absence and presence of nitrendipine, 5-methylurapidil, chloroethylclonidine and BMY 7378.

Results: The renal vasoconstrictor responses were markedly attenuated by nitrendipine and 5- methylurapidil in the diabetic rats (all P< 0.05). In the non-diabetic rats, these responses were markedly attenuated by nitrendipine, 5-methylurapidil, and BMY 7378 (all P< 0.05). In both experimental groups, chloroethylclonidine markedly accentuated the renal vasoconstrictions caused by all the adrenergic stimuli (all P< 0.05).

Conclusion: These observations indicate that alpha 1A-adrenoceptor subtypes play a major role in mediating adrenergically-induced renal vasoconstriction in the diabetic 2K1C Goldblatt hypertensive rats. In the non-diabetic 2K1C Goldblatt hypertensive rats, contributions of alpha 1A and alpha 1D-adrenoceptor subtypes were proposed. Apart from post-synaptic alpha 1-adrenoceptors, both in the diabetic and non-diabetic 2K1C Goldblatt hypertensive rats, the potential involvement of presynaptic alpha 1- adrenoceptors is also suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists*
  • Adrenergic alpha-1 Receptor Antagonists*
  • Animals
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Hypertension, Renovascular / physiopathology*
  • Kidney / blood supply*
  • Kidney / innervation
  • Kidney / physiopathology
  • Male
  • Methoxamine / pharmacology
  • Nitrendipine / pharmacology
  • Norepinephrine / pharmacology
  • Phenylephrine / pharmacology
  • Piperazines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Vasoconstriction / drug effects*

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-1 Receptor Antagonists
  • Piperazines
  • 5-methylurapidil
  • Phenylephrine
  • chlorethylclonidine
  • Nitrendipine
  • Methoxamine
  • BMY 7378
  • Clonidine
  • Norepinephrine