1991 Fiscal Year Final Research Report Summary
Abnormalities in Membrane Signal Transduction in Hypertension
| Project/Area Number |
02670405
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Wakayama Medical College |
|---|
Principal Investigator |
TSUDA Kazushi Division of Cardiology, Department of Medicine, Wakayama Medical College, 循環器内科, 助手 (90217315)
|
|---|
| Project Period (FY) |
1990 – 1991
|
| Keywords | Hypertension / Norepinephrine / Neuropeptide / Galanin / Calcitonin gene-related peptide / Membrane fluidity / Erythrocytes / Endogenous digitalis-like factor |
|---|
| Research Abstract |
In the first series of the experiments, we describe the results of studies to evaluate the effects of peptide hormones on norepinephrine (NE) release in hypertension. Neuropeptide Y (NPY) and galanin (Gal) inhibited stimulation-evoked NE release from hypothalamus and medulla oblongata of rats. A part of the mechanisms might be explained by interactions with presynaptic alpha2-adrenergic receptors and the pertussis toxin-sensitive Gi-proteins. Calcitonin gene-related peptide (CGRP) also inhibited NE release from rat brain. The CGRP-effect might be partially due to blockade of Ca^<2+>-influx through dihydropyridine-sensitive Ca^<2+>-channels in the central nervous system. In spontaneously hypertensive rats (SHR), the effect of NPY, Gal and CGRP was significantly less than in Wistar Kyoto rats (WKY). These results suggest that the peptide hormones might be involved in the regulation of sympathetic tone in the central nervous system of hypertension.
In the second series of the experiments, we examined alterations in membrane fluidity of erythrocytes in hypertension by means of an electron spin resonance (ESR) and spin labelling methods. The membrane fluidity of erythrocytes was significantly lower in SHR and in patients with essential hypertension than in the normotensive controls. The decrease in membrane fluidity in essential hypertension was correlated with endogenous digitalis-like factor in plasma. Ouabain-loading to erythrocytes decreased the membrane fluidity. The ouabain-induced change was pronounced in hypertension compared with normotensive controls. From these findings, we have drawn the conclusion that abnormalities in signal transduction and in membrane characteristics might actively participate in the pathogenesis of hypertension.
|
