Presser and mesenteric arterial hyporesponsiveness to angiotensin II is anearly event in haemorrhagic hypotension in anaesthetised rats

Objective: Vascular responsiveness to vasoconstrictors is known to be atten uated in haemorrhagic shock. In this study we assessed the temporal develop ment and the underlying mechanisms of haemorrhage-induced vascular hyporeac tivity to presser agents. Methods: In phenobarbital-anaesthetised rats hypo tension was induced by graded haemorrhage (8 ml blood total). Sham-manipula ted rats served as controls. Blood flow (BF) was recorded with ultrasonic t ransit time flow probes. Results: Following haemorrhage mean arterial press ure (MAP) fell by 25-45 mm Hg and was accompanied by a reduction in mesente ric BF without any alteration of mesenteric vascular conductance (VC). Whil e presser responses to arginine vasopressin remained unaltered, hyporespons iveness to phenylephrine (10 nmol kg(-1)) developed 120-180 min after hypot ension had been induced. Presser and mesenteric constrictor responses to an giotensin II (30 pmol kg(-1)) became significantly blunted as early as 60 m in post haemorrhage. The hypotensive effect of an angiotensin(1) receptor a ntagonist, telmisartan (1 mg kg(-1)), was likewise blunted 3 h after haemor rhage. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg k g(-1)) exaggerated the hypotensive reaction to haemorrhage but did not prev ent the development of angiotensin II hyporesponsiveness. In contrast, the nitric oxide (NO) synthase inhibitor N-G-nitro-L-arginine methyl ester (10 mg kg(-1)), as investigated 3 h post haemorrhage, restored the systemic pre sser responses to angiotensin II and phenylephrine as well as the mesenteri c 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 haemorrha ge, partially reversed haemorrhage-induced hypotension but did not modify a ngiotensin II hyporesponsiveness. Conclusion: Systemic presser responsivene ss and mesenteric arterial reactivity to endogenous and exogenous angiotens in 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. (C) 1999 Elsevier Science B.V. All rights reserved.