ENDOTHELIUM-DEPENDENT RELAXATION IN PERIPHERAL VASCULATURE AND KIDNEYOF NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Desmopressin (DDAVP), an AVP V-2-receptor agonist, evokes endothelium- dependent relaxation (EDR) due to nitric oxide (NO), EDR factor (EDRF) in the systemic vasculature, and glomerular afferent arterioles via A VP receptor(s). Glyceryl trinitrate (GTN) causes endothelium-independe nt (nonreceptor-mediated) vasodilation. We elucidated the possible inv olvement of EDRF in early non-insulin-dependent diabetes mellitus (NID DM) and glomerular hyperfiltration (GHF) by DDAVP and GTN infusions. P atients with advanced DM nephropathy (DM . Np) (n = 7) were also exami ned. DDAVP and GTN decreased the mean blood pressure in DM with GHF (D M + GHF) and without GHF (DM-GHF) greater than that in normal subjects (N), without any difference in the heart rate changes in any group. P lasma levels of cGMP, a cellular messenger of NO, were significantly i ncreased by DDAVP and GTN with a similar increment in each group. DDAV P caused a significant increase in urinary cGMP excretion in each grou p with a similar increment in each group. However, it caused a transie nt increase in creatinine clearance only in DM + GHF although GIN did not, and an exaggerated excretion of urinary albumin in early NIDDM, e specially in DM + GHF, without a change in beta(2)-microglobulin excre tion. In contrast, in DM . Np GTN caused a decrease in blood pressure and an increase in plasma cGMP levels, but DDAVP did not. In conclusio n, in peripheral vasculature and kidney, an enhanced sensitivity of va scular smooth muscle to NO is present in early NIDDM. The exaggerated dilation of glomerular afferent arterioles by preferentially produced NO in in situ, which causes a rise in P-GC, might be partly responsibl e for the glomerular hyperfiltration and subsequently the increase in the glomerular protein permeation of DM + GHF. However, in peripheral brood vessels of DM . Np EDR is impaired. Thus, EDR seems to change wi th the development of NIDDM.