title: Low concentrations of angiotensin II unmask vasoconstrictory alpha 2-adrenoceptors in isolated perfused kidneys of spontaneously hypertensive rats.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the role of vascular alpha 1- and alpha 2-adrenoceptors in kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY).
  
  
  METHODS
  SHR and WKY kidneys (12-14 weeks) were isolated and perfused with Krebs-Henseleit solution. Concentration-response curves for the alpha 1-adrenoceptor agonist methoxamine and the alpha 2-adrenoceptor agonist UK 14304 were constructed alone and in the presence of the alpha 1-adrenoceptor antagonist prazosin, the alpha 2-adrenoceptor antagonist idazoxan and exogenous angiotensin II.
  
  
  RESULTS
  Methoxamine induced a maximal pressor response of 247 +/- 9 mmHg with an EC50 of 1.3 +/- 0.1 microM in SHR and of 193 +/- 4 mmHg with an EC50 of 1.1 +/- 0.1 microM in WKY. The concentration-response curve for methoxamine was shifted to the right by prazosin with a pA2 value of 9.29 (SHR) and 9.26 (WKY) and by idazoxan with a pA2 value of 6.45 (SHR) and 6.33 (WKY). UK 14304 induced a maximal pressor response of 41 +/- 12 mmHg in SHR and of 37 +/- 8 mmHg in WKY. Angiotensin II (0.1 nM) did not significantly alter pressor responses to methoxamine but caused a marked shift to the left of the concentration-response curve for UK 14304. UK 14304 then induced a maximal pressor response of 92 +/- 13 mmHg with an EC50 of 0.07 +/- 0.01 microM in SHR and of 78 +/- 14 mmHg with an EC50 of 0.14 +/- 0.01 microM in WKY. In the presence of angiotensin II (0.1 nM) the concentration-response curve for UK 14304 was shifted to the right by prazosin with a pKB of 6.36 (SHR) and 6.33 (WKY) and by idazoxan with a pKB of 7.68 (SHR) and 7.65 (WKY).
  
  
  CONCLUSIONS
  The results demonstrate a predominant role of vasoconstrictory alpha 1-adrenoceptors over alpha 2-adrenoceptors in SHR and WKY isolated kidneys. Low physiological concentrations of angiotensin II unmask functional vascular alpha 2-adrenoceptors which are slightly more sensitive in SHR than in WKY kidneys.
authors: Medizinische Universitätsklinik Freiburg, Innere Medizin IV, Freiburg, Germany.
authors: C
authors: C
authors: Bohmann
authors: W
authors: W
authors: Rist
authors: P
authors: P
authors: Schollmeyer
authors: L C
authors: LC
authors: Rump
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D000068438:Brimonidine Tartrate; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008729:Methoxamine / Q000494:pharmacology; D010477:Perfusion; D011224:Prazosin / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D011810:Quinoxalines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D000804:Angiotensin II; D000068438:Brimonidine Tartrate; D008729:Methoxamine; D011224:Prazosin; D019329:Idazoxan