title: Pressor and mesenteric arterial hyporesponsiveness to angiotensin II is an early event in haemorrhagic hypotension in anaesthetised rats.
abstract: OBJECTIVE
  Vascular responsiveness to vasoconstrictors is known to be attenuated in haemorrhagic shock. In this study we assessed the temporal development and the underlying mechanisms of haemorrhage-induced vascular hyporeactivity to pressor agents.
  
  
  METHODS
  In phenobarbital-anaesthetised rats hypotension was induced by graded haemorrhage (8 ml blood total). Sham-manipulated rats served as controls. Blood flow (BF) was recorded with ultrasonic transit time flow probes.
  
  
  RESULTS
  Following haemorrhage mean arterial pressure (MAP) fell by 25-45 mm Hg and was accompanied by a reduction in mesenteric BF without any alteration of mesenteric vascular conductance (VC). While pressor responses to arginine vasopressin remained unaltered, hyporesponsiveness to phenylephrine (10 nmol kg-1) developed 120-180 min after hypotension had been induced. Pressor and mesenteric constrictor responses to angiotensin II (30 pmol kg-1) became significantly blunted as early as 60 min post haemorrhage. The hypotensive effect of an angiotensin1 receptor antagonist, telmisartan (1 mg kg-1), was likewise blunted 3 h after haemorrhage. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg kg-1) exaggerated the hypotensive reaction to haemorrhage but did not prevent the development of angiotensin II hyporesponsiveness. In contrast, the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (10 mg kg-1), as investigated 3 h post haemorrhage, restored the systemic pressor responses to angiotensin II and phenylephrine as well as the mesenteric constrictor responses to phenylephrine to normal level and diminished the mesenteric hyporesponsiveness to angiotensin II. Glibenclamide (20 mg kg-1), an inhibitor of ATP-sensitive K- channels given 180 min post haemorrhage, partially reversed haemorrhage-induced hypotension but did not modify angiotensin II hyporesponsiveness.
  
  
  CONCLUSIONS
  Systemic pressor responsiveness and mesenteric arterial reactivity to endogenous and exogenous angiotensin II is selectively impaired at an early stage of haemorrhagic hypotension. This phenomenon partially involves NO and is not related to ATP-sensitive K+ channels.
authors.forename: D
authors.initials: D
authors.lastname: Pieber
authors.forename: G
authors.initials: G
authors.lastname: Horina
authors.forename: A
authors.initials: A
authors.lastname: Sandner-Kiesling
authors.forename: T R
authors.initials: TR
authors.lastname: Pieber
authors.forename: A
authors.initials: A
authors.lastname: Heinemann
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D000077333:Telmisartan; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001565:Benzoates; D016861:Cyclooxygenase Inhibitors; D015221:Potassium Channels; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D010656:Phenylephrine; D009569:Nitric Oxide; D005905:Glyburide; D000077333:Telmisartan; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin