Endothelium-dependent relaxation in peripheral vasculature and kidney of non-insulin-dependent diabetes mellitus

Kenichi Yamada, Hirofumi Nakano, Masaaki Nakayama, Osamu Nozaki, Yasuhiko Miura, Motonobu Nishimura, Hiroki Tsuchida, Nobuhide Mimura

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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 β2-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.

Original languageEnglish
Pages (from-to)203-207
Number of pages5
JournalJournal of Diabetes and Its Complications
Volume9
Issue number4
DOIs
Publication statusPublished - 1995 Jan 1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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