Interference of angiotensin II and enalapril with hepatic blood flow regulation

Abstract

Acute reduction of portal vein blood flow (Qpv) increases hepatic arterial perfusion (Qha) [the hepatic arterial buffer response (HABR)]. Angiotensin II (AT-II) reduces Qpv, but its effect on HABR is not known. We explored interactions of AT-II and enalapril with hepatic blood flow regulation. Twenty healthy anesthetized pigs were randomized to receive AT-II (n = 8) from 5 to 61 ng/kg per min, enalapril (n = 8) from 3 to 24 μg/kg per h, or saline (n = 4). HABR was assessed by occluding portal vein and expressed as 1) ratio between changes in Qha and Qpv, 2) hepatic arterial conductance (Cha). AT-II infusion increased mean arterial blood pressure from 74 (66-77) mmHg to 116 (109-130) mmHg (median, IQR; P < 0.0001) and decreased cardiac output, Qpv, and renal artery flow (-24%, -28% and -45%, respectively). The fraction of cardiac output of Qha, carotid, and femoral flows increased. With enalapril, blood pressure decreased, whereas cardiac output was maintained with flow redistribution favoring hepatic and renal arteries. In AT-II group, dQha/dQpv increased from 0.06 (0.03, 0.17) to 0.24 (0.13, 0.31) (P = 0.002), but Cha during acute portal vein occlusion decreased from 4.3 (1.6, 6.6) to 2.9 (1.2, 3.7) ml/mmHg (P = 0.003). Both variables remained unchanged in the enalapril group and in controls. AT-II infusion reduces portal flow in parallel with cardiac output and induces a dose-dependent redistribution of flow, favoring brain, hepatic artery, and peripheral tissues at the expense of renal perfusion. During HABR, AT-II decreases Cha but increases Qha compensation, likely as result of increased hepatic arterial perfusion pressure. Enalapril had no effect on HABR.

Angiotensin II in Septic Shock

“…Our data demonstrate that the effects of angiotensin II on regional perfusion are different in vasodilatatory states compared to normal conditions: in healthy pigs, angiotensin II infusion resulted in net reduction of renal blood flow, while portal blood flow decreased in parallel with cardiac output, and fractional blood flow increased dose-dependently in carotid, hepatic and femoral arteries [38]. As in sepsis, angiotensin II infusion had no effects on diuresis or creatinine clearance [38].…”

“…As in sepsis, angiotensin II infusion had no effects on diuresis or creatinine clearance [38]. The discrepant findings on renal perfusion can be explained by sepsisinduced hyporeactivity of the renal arteries [39].…”

Angiotensin II in septic shock

“…Our data demonstrate that the effects of angiotensin II on regional perfusion are different in vasodilatatory states compared to normal conditions: in healthy pigs, angiotensin II infusion resulted in net reduction of renal blood flow, while portal blood flow decreased in parallel with cardiac output, and fractional blood flow increased dose-dependently in carotid, hepatic and femoral arteries [ 38 ]. As in sepsis, angiotensin II infusion had no effects on diuresis or creatinine clearance [ 38 ]. The discrepant findings on renal perfusion can be explained by sepsis-induced hyporeactivity of the renal arteries [ 39 ].…”

Vasopressor Therapy and the Brain: Dark Side of the Moon

“…The adjunctive administration of vasopressin in sepsis did not alter the number of days alive without neurological dysfunction (119). The systemic administration of moderate doses of angiotensin II to healthy pigs increases carotid blood flow; the effect on cerebral blood flow was not reported (120). The systemic administration of high doses of angiotensin to healthy baboons lead to disruption of the blood brain barrier and to ischemic brain lesions (121).…”