Endothelium-dependent relaxation in peripheral vasculature and kidney of non-insulin-dependent diabetes mellitus.
Desmopressin (DDAVP), an AVP.V2-receptor agonist, evokes endothelium-dependent relaxation (EDR) due to nitric oxide (NO), EDR factor (EDRF) in the systemic vasculature, and glomerular afferent arterioles via AVP receptor(s). Glyceryl trinitrate (GTN) causes endothelium-independent (nonreceptor-mediated) vasodilation. We elucidated the possible involvement of EDRF in early non-insulin-dependent diabetes mellitus (NIDDM) and glomerular hyperfiltration (GHF) by DDAVP and GTN infusions. Patients with advanced DM nephropathy (DM.Np) (n = 7) were also examined. DDAVP and GTN decreased the mean blood pressure in DM with GHF (DM + GHF) and without GHF (DM-GHF) greater than that in normal subjects (N), without any difference in the heart rate changes in any group. Plasma levels of cGMP, a cellular messenger of NO, were significantly increased by DDAVP and GTN with a similar increment in each group. DDAVP caused a significant increase in urinary cGMP excretion in each group with a similar increment in each group. However, it caused a transient increase in creatinine clearance only in DM + GHF although GTN did not, and an exaggerated excretion of urinary albumin in early NIDDM, especially in DM+GHF, without a change in beta 2-microglobulin excretion. In contrast, in DM.Np GTN caused a decrease in blood pressure and an increase in plasma cGMP levels, but DDAVP did not. In conclusion, in peripheral vasculature and kidney, an enhanced sensitivity of vascular 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 PGC, might be partly responsible for the glomerular hyperfiltration and subsequently the increase in the glomerular protein permeation of DM+GHF. However, in peripheral blood vessels of DM.Np EDR is impaired. Thus, EDR seems to change with the development of NIDDM.
Yamada
K
K
Division of Clinical Research, Sakura National Hospital, Chiba, Japan.
Nakano
H
H
Nakayama
M
M
Nozaki
O
O
Miura
Y
Y
Nishimura
M
M
Tsuchida
H
H
Mimura
N
N
D000328:Adult; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000098:blood supply; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000652:urine
D001613:beta 2-Microglobulin; D009569:Nitric Oxide; D003404:Creatinine; D003894:Deamino Arginine Vasopressin; D005996:Nitroglycerin; D006152:Cyclic GMP