Effects of Angiotensin I and Angiotensin II on Canine Hepatic Vascular Resistance

Abstract

The effects of angiotensin I (0.2-3.2 ju.g) and angioteasin II (0.1-1.6 fig) injections into the pump-perfused arterial supply of the liver were studied in dogs anesthetized with sodium pentobarbital. Marked increases in hepatic artery perfusion pressure (10-50%), reflecting directicnally similar changes in resistance to blood flow, were caused by either angiotensin I or angiotensin II. Resistance increases produced by angiotensin I were significantly attenuated by the synthetic nonapeptide SQ 20881 (Pyr-Trp-Pro-Arg-Pro-Gln-Iie-Pro-Pro, 50 j«,g/kg, iv) that inhibits enzymatic conversion of angiotensin I to ang:otensin II. In contrast; responses caused by angiotensin II were unaltered by SQ 20881. However, resistance increases caused by either angiotensin I or angiotensin II were blocked by 1-Sar-8-Ala-angiotensin II (100 /ug/kg mirr 1 , ia), a specific angiotensin II antagonist. These findings parallel the finding that responses to angiotensin I in the vasculature supplied by the hepatic artery are largely caused by local enzymatic conversion of angiotensin I to angiotensin II. Such conversion appears to occur to the extent of about 46$. importantly involved in local regulation of blood flow.We examined the effects of angiotensin I and angiotensin II on vascular resistance to blood flow in the vasculature supplied by the hepatic artery with and without a new inhibitor of the angiotensinconverting enzyme and with and without an angiotensin II antagonist. MethodsFourteen mongrel dogs of either sex (14-17 kg), anesthetized with sodium pentobarbital (30 mg/kg, iv), were intcbated with a cuffed endotracheal tube and permitted to breathe spontaneously. Systemic arterial blood pressure was measured with a catheter inserted into the right femoral artery and advanced into the thoracic cavity until its tip was close to the heart (Narco P-1000A pressure transducer).The left common carotid artery was exposed in the cervical region and carefully separated from the vagal nerve. A laparotomy was used to expose the hepatic artery. After all surgery was completed, heparin (500 units/kg, iv) was administered to prevent blood clotting. Blood from the left common carotid artery was diverted through a peristaltic Sigmamotor pump (T8) and used to perfuse the hepatic artery at a constant flow rate. Blood flow through the pump-perfused hepatic artery ranged between 70 and 90 ml/min in different dogs. In each experiment the pump was adjusted so that perfusion pressure was about 85% of systemi;: arterial blood pressure; preliminary studies

Action of Tonin on the Response of Rat on Mesenteric Vessels to Norepinephrine

“…The percentage of conversion rate of angiotensin I into angiotensin I1 in the perfused rat mesenteric arteries, which was calculated according to the method reported by Di Salvo et al (16), was between 3.3 and 14.7%. This percentage of conversion rate was in accordance with that reported in other vascular tissues (16)(17)(18)(19). Our results confirmed the observations of Malik and Jasjletti (8) that both angiotensins I and I1 potentiated the vasoconstrictor response of isolated perfused rat mesenteric arteries to injected norepinephrine.…”

Contractile Responses to Angiotensin l and Angiotensin II in Hamster Uterine Smooth Muscle

“…4). In contrast, 1-Sar-8-Ala-angiotensin 11, a well-characterized A-I1 antagonist (7,8,16), specifically blocked responses to A-I1 (Figs. 3 and 4).…”

“…3 and 4). Third, responses to A-I were nearly eliminated by SQ 20881 (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro), which is a potent inhibitor of angiotensin-converting enzyme (7,8). In sharp contrast, SQ 20881 did not alter responses to A-I1 or KCl (Figs.…”

“…Angiotensin-converting enzyme was inhibited by SQ-2088 1 (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) and P-1 13 ( I-Sar-8-Ala-A-11) was used to block A-I1 receptors (7,8,16). Cholinergic blockade was produced with atropine, whereas a-adrenergic blockade was produced with phentolamine.…”

Mechanism of angiotensin I converting enzyme inhibition by SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) in vivo. Further evidence for extrapulmonary conversion.

“…Previous studies in which AI was administered into various peripheral capillary beds of the dog, including kidney, 24 ' M mesentcric circulation, 2 " hindlimb 27 and liver, 28 have given evidence that some AI conversion occurs in extrapulmonary sites. Also, the presence of all components of the renin-angiotensin system has been reported in isolated tissues not perfused with blood.…”