ACE Inhibitors and Renal Vascular Responses in the Spontaneously Hypertensive Rat

BACKGROUND: Substantial evidence has accumulated for the intrarenal generation of functionally important quantities of angiotensin II (Ang II). To assess the possibility that Ang II generation occurs beyond a barrier to diffusion from the vascular compartment, six angiotensin-converting enzyme (ACE) inhibitors varying widely in their lipid solubility were employed in the spontaneously hypertensive rat (SHR) and their normotensive controls (WKY). The biological end points were renal blood flow and its response to Ang II. RESULTS: Two ACE inhibitors, ramipril and captopril, induced a larger increase in renal blood flow and enhanced the renal vascular response to Ang II substantially more than did enalapril and lisinopril. The two prodrugs, enalapril and ramipril, which are substantially more lipophilic than the respective active drugs, enalaprilat and ramiprilat, showed equivalent responses. The partial agonist saralasin virtually abolished the renal vasodilator response to ramipril. The pattern of response was similar in WKY, but the responses were substantially smaller. CONCLUSIONS: The results support the concept that a functionally important compartment for intrarenal Ang II formation exists in the healthy rat and that this process is amplified in the SHR.