Differential regional hemodynamic effects of corticotropin in conscious sheep.

Abstract

The regional hemodynamic effects of 5 days of intravenous infusion of corticotropin (ACTH) (5 /xg/kg per day) were examined in conscious sheep (n=8). Mean arterial pressure increased from 81 ±2 to 93±3 mm Hg (/><.001) on day 2 of ACTH and remained at this level during the infusion. Cardiac output increased from 5.13±0.19 to 6.06±0.33 L/min (/ ) <.O1) because of an increase in stroke volume from 65±4 to 79±8 mL per beat (P<.01); heart rate remained unchanged. ACTH did not alter total peripheral conductance but had differential effects on regional conductances. Mesenteric conductance fell from 5.8±0.2 to a minimum of 4.9±0.3 (mL/min)/mm Hg (P<.05), and renal conductance increased from 3.5±0.3 to 4.6±0.3 (mL/min)/ mm Hg (P<.001). There was a small increase in iliac conductance (f<.05) and no change in coronary conductance. Mesenteric and iliac conductances fell progressively over 24 to 48 hours, whereas renal conductance increased rapidly after 3 hours of ACTH, reaching a maximum after 6 hours. Renal blood flow was increased during ACTH infusion from 278±18 to 403±23 mL/min (P<.001); mesenteric C orticotropin (ACTH) administration increases blood pressure in both humans 1 -3 and experimental animals. 46 In conscious sheep intravenous infusion of ACTH results in an increase in arterial blood pressure within 24 hours, which is sustained as long as ACTH is infused over a 5-to 10-day period. 7 ACTH hypertension can be reproduced by infusion of a combination of adrenocortical steroids and is dependent on the presence of the adrenal glands but not on intact adrenal innervation. 48 The hypertension is associated with an increase in plasma volume, without a significant change in extracellular fluid volume.9 A volume component of the hypertension is also suggested by the finding that the ACTH-induced rise in blood pressure can be modulated by alterations in sodium status. Long-term sodium loading magnifies the pressure rise produced by ACTH, and long-term dietary sodium restriction blunts the rise.10 " The hemodynamic profile of ACTH hypertension in conscious sheep is characterized by an elevated cardiac output (CO), with no change in total peripheral resistance. peripheral resistance to remain constant in the presence of renal vasodilatation, vasoconstriction must be occurring in other vascular beds. In the present study the effect of ACTH infusion on regional hemodynamics was examined in conscious sheep instrumented with electromagnetic flow probes to measure CO and with transittime flow probes to measure regional arterial blood flows. The aim of the study was to examine the regional hemodynamic effects of ACTH and to determine whether ACTH acts selectively to cause vasoconstriction in one vascular bed or whether the vasoconstriction is a more generalized phenomenon. MethodsMerino cross ewes (35-to 45-kg body weight), oophorectomized and with carotid artery loops, were housed in metabolism cages in association with other sheep. They were not used for at least 4 weeks after surgery until they were accustomed to ...

Altered cardiovascular haemodynamics and baroreceptor‒heart rate reflex in adult sheep after prenatal exposure to dexamethasone

“…This type of hypertension, which is dependent on increased CO, is similar to that found with cortisol-and corticotropin (' ACTH ')-induced hypertension in humans and sheep [17,[19][20][21][22][23]. In addition, the increase in CO was due to an increase in stroke volume, not in HR.…”

Altered cardiovascular haemodynamics and baroreceptor–heart rate reflex in adult sheep after prenatal exposure to dexamethasone

“…The increase in stroke volume could result from an increase in ventricular contractility due to cardiac hypertrophy, or from an increased preload (increase in plasma volume). This type of hypertension, which is dependent on increased CO, is similar to that found with cortisol-and corticotropin (' ACTH ')-induced hypertension in humans and sheep [17,[19][20][21][22][23]. This raises the possibility that prenatal dexamethasone could have altered permanently the level of one or more steroids, or of their receptors, which would ultimately lead to hypertension.…”

Species Variability in Cardiovascular Research: The Example of Adrenocorticotrophin‐induced Hypertension

“…β‐Adrenoceptor blockade did not prevent the rise in cardiac output or the rise in blood pressure, 37 but both nisoldipine and minoxidil prevented the development of the increase in blood pressure 30 . Subsequent studies confirmed these changes (rise in cardiac output, no change in total peripheral conductance) 38 . The unchanged total peripheral conductance reflected regional alterations, with falls in mesenteric and iliac conductances and a rise in renal conductance 38 consistent with increased mesenteric and iliac resistances and decreased renal resistance.…”