Effect of Angiotensin Converting Enzyme Inhibition on Renal Autoregulation

Abstract

The mechanisms responsible for renal autoregulation continue to arouse considerable interest, and much of the present controversy is centered upon the role of the renin-angiotensin system in modulating the renal hemodynamic response to alterations in renal arterial pressure. Britton proposed a renin-renal autoregulation hypothesis which postulated that plasma angiotensinogen (renin substrate) and converting enzyme interact with cytoplasmic renin at the luminal surfact of the wall of the afferent arteriole to affect the arterial tone (1). In an earlier study, Waugh and Shanks observed that perfusion of isolated kidneys with an artificial colloidal perfusate resulted in loss of autoregulation, while the addition of fresh plasma to the perfusate restored the autoregulatory phenomenon (2). If the renin-angiotensin system is responsible for renal autoregulation and the presence of angiotensin converting enzyme is an essential participant in the autoregulatory process, then the infusion of an angiotensin converting enzyme inhibitor into the renal circulation should modify renal autoregulation. The current study was designed to evaluate the effects on renal autoregulation of limiting the conversion of angiotensin I to angiotensin I1 during a reduction in renal perfusion pressure.Methods. Experiments were performed on 15 female dogs (wt: 19.2 * 1.2 kg) anesthetized with intravenous pentobarbitol (30 mg/ kg) and placed on a positive pressure respirator .l During surgical preparation an infu-sion of Ringers solution was started and approximately 400 ml administered over 2 hr to replace fluid losses. Catheters were introduced into both ureters via a suprapubic incision and a femoral artery was cannulated to withdraw blood samples as well as to monitor blood pressure. The left kidney was exposed through a retroperitoneal flank incision and with a minimum of dissection the aorta, left renal artery and ovarian vein were exposed. A modified Blalock clamp (3) was applied loosely across the aorta cephalad to the right renal artery. The ovarian vein was cannulated with a length of Teflon tubing and the tip advanced to the orifice of the renal vein. The curved shaft of a #25 gauge needle, attached to two lengths of tubing by a ''Y" connection, was inserted into the left renal artery for infusion of 0.9% saline solution, angiotensin I, and angiotensin converting enzyme inhibitor (SQ20881)2 at a rate of 0.5 ml/min. A minimum of 2 hr was allowed to elapse for recovery following the surgical procedures. During this interval appropriate priming and maintenance infusions of p-aminohippurate (PAH) and 1251-iothalamate (Abbott Laboratories, No. Chicago, Ill.) were administered and 30-45 min were allowed for equilibration of these substances before urine collection periods of 20 min duration were started. Blood samples from the femoral artery and renal vein were withdrawn 3 min before the mid point of each period.To determine the effectiveness of the intra-~ ~ ~ ~~

Whole Kidney Response to Reduced Arterial Pressure during Converting Enzyme Inhibition in the Rat

“…There seems to be general agreement that RAS plays only a minor role in the autoregu lation of RBF [Johns, 1979], while reports have been conflicting with regard to the par ticipation of RAS in the regulation of GFR during changes in RAP [Gagnon et al, 1974;Hall et al, 1977].…”

Renal Autoregulatory Efficiency during Angiotensin-Converting Enzyme Inhibition in Dogs on a Low Sodium Diet

“…Studies evaluating redistribution have shown differ ent results in different laboratories. In renindepleted dogs or during C E I, a reduction in RAP redistributed flow away from the outer cortex [10,26]. Other investigators have observed little or no changes in cortical flow distribution in normal and renin-depleted animals, when the R A P was lowered [27][28][29].…”

“…and urinary sodium excretion rates in dogs previously maintained on a sodi um-restricted diet [14,16]. In spite o f the increases in RBF, there was a well-main tained and highly efficient capability to autoregulate R B F in response to reductions in R A P [10][11][12][13][14], In fact, autoregulatory behavior was actually enhanced, since RBF was autoregulated with a high degree o f effi ciency down to RAP values lower than during control conditions; in some cases, there were increases in R BF at the lower values o f RAP. Also, the average G F R values shown in ta ble II indicate that there were no significant differences in G F R obtained at the four RAP ranges evaluated during the CEI period.…”

A Comparison of the Ability of Two Angiotensin Ii Receptor Blocking Drugs, 1‐sar, 8‐ala Angiotensin Ii and 1‐sar, 8‐ile Angiotensin Ii, to Modify the Regulation of Glomerular Filtration Rate in the Cat

“…This is consistent with the earlier findings observed with SQ20,881 administration in the cat (Johns, 1979) and those of Abe, Kishimoto & Yamamoto (1976), Anderson et al (1975), Kimbrough, Vaughan, Carey & Ayres (1977) in the dog and Arendshorst & Finn (1977) in the rat which suggest that under normal dietary sodium conditions renal blood flow is very little influenced by circulating angiotensin II. However, it is clear that in states where the plasma levels of angiotensin II are raised, such as following low dietary sodium (Gagnon, Rice & Flamenbaum, 1974;Kimbrough et al, 1977;Hall et al, 1977bHall et al, , 1979 or inferior vena caval constriction (Freeman, Davis, Vitale & Johnson, 1973) angiotensin II can greatly influence the rate of renal blood flow.…”