Contribution of humoral systems to the recovery of blood pressure following severe haemorrhage.
1. Profound haemorrhage activates a number of pressor mechanisms, including the release of catecholamines, angiotensin II and arginine-vasopressin, which contribute to the subsequent cardiovascular recovery. Using specific single or combined blockade with prazosin, losartan and Manning compound (AVPX), the aim of this study was to evaluate the involvement of the three pressor systems in blood pressure recovery following severe haemorrhage (20 ml kg-1). 2. Haemorrhage of conscious, unrestrained rats resulted in a significant initial decrease in blood pressure of approximately 60 mmHg, and heart rate of approximately 70 bpm. Then, blood pressure tended to return to the control level within 10 min. The total cardiovascular recovery corresponded to increments of 52 +/- 5 mmHg (81% of the acute fall) for systolic blood pressure, and of 92 +/- 22 bpm (124%) for heart rate at 60 min post-bleeding. Significant falls in haematocrit (-10.5 +/- 1.2%, P < 0.01), in plasma concentrations of proteins (-10.3 +/- 0.9 g l-1, P < 0.01) and haemoglobin (-2.58 +/- 0.72 g 100 ml-1, P < 0.05) were observed at 60 min post-bleeding. 3. Pretreatment with one or two specific antagonists did not exaggerate the initial fall in blood pressure. The initial bradycardia was weakened only by combined blockade with losartan and AVPX. 4. The blood pressure recovery from a haemorrhage was delayed by approximately 25 min by the inhibition of vasopressin activity. The systolic blood pressure recovery in control animals (81% of the acute fall) was blunted by losartan (55% of the acute fall), prazosin (49%), combined losartan and AVPX (36%), prazosin and AVPX (36%), and also by prazosin plus losartan (13%). The diastolic blood pressure recovery was blunted only in the groups where the activity of angiotensin II was inhibited by losartan. 5. In conclusion, we have shown that neither catecholamines, angiotensin II nor vasopressin, although activated, individually compensate the acute hypotensive response to haemorrhage. The contribution of vasopressin to the blood pressure recovery post-bleeding is transient and is rapidly replaced by the pressor activity of the catecholamines and angiotensin II. The full systolic blood pressure recovery from severe haemorrhage requires the combined activity of these two pressor systems, while the diastolic blood pressure recovery seems to be only dependent upon angiotensin II activity.
Ponchon
P
P
Laboratory of Pharmacology, CNRS URA 1482, Faculty of Medicine Necker, Paris, France.
Elghozi
J L
JL
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000037:antagonists & inhibitors / Q000502:physiology*; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006470:Hemorrhage / Q000503:physiopathology*; D006727:Hormone Antagonists / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013599:Systole / Q000187:drug effects / Q000502:physiology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D002395:Catecholamines; D006727:Hormone Antagonists; D018340:Receptors, Adrenergic, alpha-1; D000804:Angiotensin II; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D019808:Losartan; D011224:Prazosin