Cardiovascular and endocrine response to hemorrhage after alpha 1-blockade in lambs and ewes

Abstract

To evaluate the role of the alpha 1-adrenergic system in the response to hemorrhage during development, lambs and adult sheep were chronically catheterized and hemorrhaged after pretreatment with prazosin or vehicle. The adults became markedly more hypotensive after alpha 1-blockade and hemorrhage than after vehicle and hemorrhage (26.1 +/- 4 vs. 10.7 +/- 2%, P less than 0.0001), whereas the lambs were no more hypotensive when hemorrhaged after prazosin (21.5 +/- 3.2 vs. 23.1 +/- 4.4%, P greater than 0.05). In the adults and the lambs, hemorrhage produced elevations in plasma renin activity and arginine vasopressin. However, after prazosin, the adults had a far greater increase in arginine vasopressin levels than after vehicle treatment (1,970 +/- 820 vs. 320 +/- 273%).

Renin and Heart Rate Responses to Haemorrhage are Age Dependent in Conscious Lambs

“…Along with our present observations in newborn and older sheep, it seems that haemorrhage is associated with age-dependent alterations in the arterial baroreflex control of heart rate, although this premise is speculative and requires additional investigation. Activation of the renin-angiotensin system occurs during the non-hypotensive phase of haemorrhage in conscious adult sheep (Cameron et al 1984;Block et al 1987;Starc & Stalcup, 1987;Ullman et al 1993), as well as other species; this response is thought to contribute to the cardiovascular responses to haemorrhage. In the present experiments, the renin response to haemorrhage occurred at a lesser degree of blood loss early in life.…”

“…Any age-dependent effects of haemorrhage on the biosynthesis or release of these or other vasodilatory factors is not known. In conscious adult sheep (Cameron et al 1984;Block et al 1987), dogs (Wang et al 1983) and monkeys (Arnauld et al 1977), haemorrhage also results in an increase in plasma levels of AVP, during the hypotensive phase of haemorrhage. This suggests that AVP may contribute predominantly to promoting the recovery from haemorrhagic hypotension, playing a less important role in regulating arterial pressure during mild to moderate haemorrhage, at least in adult animals.…”

Central α-1-Adrenergic Control of Vasopressin Secretion in Newborn Lambs

“…We did not observe a similar effect in the neonatal lambs treated with i.v. prazosin (2) where the change in blood pressure induced by hemorrhage was only 14% in the prazosin-treated lambs and was probably too small to result in large increases in AVP levels.…”

“…This observation led us to hypothesize that hypothalamic a-1 receptors exert an inhibitory influence on the secretion of AVP in response to hypotension in the near-term lamb fetus. In the neonatal lamb, AVP levels after hemorrhage were similar with prazosin and with vehicle, but the relative decrease in blood pressure was less in the prazosin-treated lambs and may have been subthreshold for the secretion of AVP (2). To prove our hypothesis, we designed an experiment in which CNS a-1 adrenoceptor blockade was achieved in the newborn lamb by ICV injection, rather than i.v.…”

“…These results differ from observationsh adult rats and dogs and may be accounted for by developmental or species differences. (Pediatr Res 30: 50-54,1991) Abbreviations AVP, arginine vasopressin CSF, cerebrospinal fluid HR, heart rate ICV, intracerebroventricular MABP, mean arterial blood pressure PE, phenylephrine PRA, plasma renin activity AVP has been shown to have a role in fetal and neonatal cardiovascular homeostasis as a "stress" hormone (1)(2)(3). Neonatal and fetal AVP secretion may be induced by hypoxia, hypotension, and acidosis.…”