Background: 

Endothelium-dependent vasodilation is mediated by nitric oxide (NO), prostaglandins (PG), and endothelium-derived hyperpolarizing factor (EDHF). We sought to clarify the temporal characteristics of these three components in the vasodilator response to acetylcholine (Ach) in the kidney.

Methods: 

Renal vascular resistance (RVR) was studied in anesthetized rats in response to bolus injections of 100 ng Ach into the renal artery before and after inhibition of the production of NO by LNAME or PG by indomethacin (INDO), or both. NO- and PG-components were derived by subtraction of the Ach-response during LNAME or INDO alone from that of its paired control. The remainder after LNAME+INDO was ascribed to EDHF.

Results: 

During control, Ach reduced RVR by a maximum of 30±1% (DRVRmax) from baseline. Integrated over 240 s after injection, the response amounted to 2264±164%s (DRVRint, =% RVR change x time). The effect reached its maximum at Tmax=30±2 s after its beginning and RVR had recovered to 5% below baseline at Trec=126±10 s. During LNAME+INDO (=EDHF-component), DRVRmax was 13±1% and DRVRint 433±73%s. Tmax was reached faster at 16±1s and Trec at 36±3 s. LNAME and INDO alone each diminished the response. The time course of the difference caused by LNAME in each animal (=NO-component) reached DRVRint of 1517±193%s, Tmax at 40±5 s, and Trec at 112±16 s. The difference due to INDO (=PG-component) showed DRVRint of 596±119%s, Tmax at 25±8 s, and Trec at 84±24 s.

Conclusions: 

Ach-induced vasodilation in the kidney is mediated predominantly by NO (>50%) and less so by PG (~25%) and EDHF (~20%). EDHF is substantially faster than NO, PG-kinetics seem intermediate. - Supported by FRIAS, Universität Freiburg.