Effect of the Synthetic Peptide, SQ 20,881, on Distribution of Blood Flow in the Rat

Abstract

Angiotensin I1 is a potent vasoconstrictor agent which will produce changes in renal blood flow. Since the renin-angiotensin system has been implicated in the control of renal hemodynamics (1, 2 ) , it is important to determine if angiotensin I1 has a preferential action on the kidney. Recently, several peptides which inhibit the conversion of angiotensin T to angiotensin I1 have become available ( 3 ) . Reports indicate that these peptides are active in vivo, and effectively block the pressor response following injection of angiotensin I. We have utilized one of these peptides (SQ 20,881)3 to study the redistribution of blood flow to several organs in the rat. Materials and Methods. At least 4 daysprior to the actual experiments, a polyethylene catheter was implanted into the left ventricle or ascending aorta via the right carotid artery in 250-300 g female rats. On the day of the experiment, the animals were anesthetized with pentobarbital sodium ( 60 mg,/kg) and the ventricular catheter was exposed and flushed with saline. A femoral vein was cannulated for injection of SQ 20,881, and a femoral artery was cannulated to measure mean systemic blood pressure using a strain gauge pressure transducer (Statham P23Dd) and Grass polygraph or Beckman dynograph.Blood flow redistribution was determined in the intestine, liver, kidneys, spleen, adrenals, stomach and skeletal muscle. blood flow in this organ from animal to anin-ma1 was found to be too great to yield valid results, In addition, similar studies were performed on three pregnant rats in order to observe the possible effects of the peptide in this situation.Radioactive microspheres (3M Co.) with a diameter of 15 pm and labeled with either ICr)Yb or 8*iSr were used. The microspheres were diluted in a glucose solution with a density of 1.3 g/cm3 which is the same as the density of the spheres. After injection of the microspheres, the animals were killed and the organs or pieces of organs were counted in a two-channel well-type scintillation counter.In control experiments, microspheres were injected in random order and the distribution was calculated for the first and second injection. In experimental animals, SQ 20,881, in doses of 4 or 40 mg/kg, was given between the two injections of microspheres. The injection of microspheres was again randomized and distribution was calculated before and after administration of the peptide.Percentage distribution of microspheres in various organs was calculated as the counts per minute of either Yb or Sr in a given organ divided by the total counts to all of the organs. The data were analyzed using the Student's t test with a .05 probability level of significance.In order to test the effectiveness of the peptide in inhibiting angiotensin I converting enzyme activity, various doses of angiotensin I and angiotensin I1 were administered intravenously to 250-300 g rats. The changes in blood pressure were recorded and SQ 20, 881 administered. The animals were then injected with identical doses of angiotensin I and angiotensin I1 an...

Acute renovascular hypertension in conscious dogs. Interaction of the renin-angiotensin system and sympathetic nervous system in systemic hemodynamics and regional blood flow responses.

“…Thus, exogenous angiotensin increases local resistance more in the renal and coronary vessels (Barbour and Bailie, 1973;Hollenberg et al, 1974;Heyndricks et al, 1976) whereas adrenergic stimulation exerts a greater constricting effect in the muscular and cutaneous vessels (Mark et al, 1972). The changes observed in the present study represent the first account of what happens after acute stimulation of renin secretion with elevation of endogenous angiotensin and catecholamines, and they confirm that endogenous vasoactive factors as well exert a selective effect in different vascular beds.…”