Urn1 Res (1996) 24:217-227 9 Springer-Verlag 1996 J. Frokia~r.J.C. Djurhuus.M. Nielsen E. B. Pedersen Renal hemodynamic response to ureteral obstruction during converting enzyme inhibition Received: 24 May 1995 / Accepted: 28 December 1995 Abstract Acute unilateral obstruction (UUO) of the pig kidney is associated with an increased secretion of intrarenally generated angiotensin II (ANG II). In or- der to clarify the importance of this intrarenal ANG II generation during acute UUO, ipsilateral and con- tralateral renal blood flow and renal secretion rate of ANG II were determined in pigs during continuous infusion of an angiotensin I converting enzyme (ACE) inhibitor. Pigs were operatively equipped with electro- magnetic flow probes and catheters in the renal veins and aorta. Intravenous administration of the ACE in- hibitor SQ14 225 (captopril), 1 mg/kg per hour, resulted in a significant increase in renal blood flow in the contralateral kidney from 340 _+ 28 ml/min to 435 _+ 36 ml/min (P < 0.01), whereas renal blood flow in the ipsilateral kidney was significantly reduced from 388 _+ 23 ml/min to 248 __ 24ml/min, similar to the reduction in controls. Captopril reduced mean aortic blood pressure, renal vascular resistance consistently on both sides, and plasma concentrations of ANG II and aldosterone from all sample sites. Renal secretion rate of ANG II showed a clear tendency to be reduced from the ipsilateral kidney. The results suggest that in UUO a compensatory increase in renal blood flow may be inhibited in part due to an enhanced secretion of ANG II in the ipsilateral kidney. However, a captopril- mediated inhibition of bradykinin breakdown may also explain some of the observed changes. Key words Pigs- Obstructive nephropathy. Renal blood flow. Renal vascular resistance" Blood pressure- J. Froki~er (l~). J. C. Djurhuus. M. Nielsen Institute of Experimental Clinical Research, Skejby University Hospital, DK-8200 Aarhus N, Denmark E. B. Pedersen Department of Medicine and Nephrology C, Skejby University Hospital, DK-8200 Aarhus N, Denmark Angiotensin II. Angiotensin I converting enzyme inhibition Introduction Following complete unilateral ureteral obstruction (UUO), renal blood flow (RBF) is reduced [27]. This reduction is thought to be caused by active vasocon- strictor mechanisms within the kidney vasculature in- creasing renal vascular resistance (RVR) [7]. The role of angiotensin II (ANG II) as a mediator of this in- creased RVR in ureteral obstruction has previously been investigated [-2, 21, 30]. Moreover, there is now substantial evidence to indicate that all of the compo- nents necessary for the local formation of ANG II exist in the kidney, and they operate in whole or in part, independently of the circulating renin angiotensin sys- tem (RAS) [1, 12, 13, 19, 25]. A pig model with acute unilateral complete ureteral obstruction enables us to study renal extraction of hormones from both the obstructed kidney (OK) and the contralateral intact kidney (CLK) together with continuous monitoring of renal blood flow, and in a previous study we demonstrated an increased in- trarenal ANG II generation in response to short-term UUO [9]. In addition to its effect on the obstructed kidney, it has been suggested that ANG II also plays a role in the CLK during and after relief of obstruction in the rat [-5, 6]. In the neonatal rat, UUO results in a prompt increase in the ipsilateral renal juxtaglomeru- lar granulation index, as well as a delayed increase in the granulation index of the intact kidney [-5]. Similar to the results from our recent study [9], E1-Dahr et al. found elevated levels of both ANG I and ANG II 1 week after UUO [6]. In addition, renal angiotensin- converting enzyme (ACE) activity was elevated in both the OK and CLK during prolonged UUO [-6]. Taken together, previous investigations suggest a major role for ANG II during the early phase of development of