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Deficient activity of stimulatory nucleotide-binding regulatory protein in lymphocytes from patients with essential
H Yoshikawa1, K Fukuda, Y Wanaka
1Department of Medicine, Wakayama Medical College, Japan.
Insights
Essential hypertension patients show reduced stimulatory G-protein activity in lymphocytes. This cardiovascular beta-adrenoceptor-adenylate cyclase system defect may contribute to hypertension pathogenesis.
Area of Science:
- Cardiovascular Physiology
- Cellular Signaling
- Hypertension Research
Background:
- Lymphocytes serve as a model for studying the cardiovascular beta-adrenoceptor-adenylate cyclase system.
- Essential hypertension is a complex condition where cellular signaling pathways may be altered.
Purpose of the Study:
- To investigate the role of the beta-adrenoceptor-adenylate cyclase system in essential hypertension.
- To compare signaling pathway activity in lymphocytes from hypertensive patients and normotensive controls.
Main Methods:
- Radioligand binding assays using 125I-cyanopindolol to quantify beta-adrenoceptor number and affinity.
- Measurement of cyclic adenosine monophosphate (cAMP) accumulation in response to isoproterenol, cholera toxin, and forskolin.
Main Results:
- No significant differences in beta-adrenoceptor concentration or affinity between hypertensive and normotensive groups.
- Reduced cAMP accumulation in response to isoproterenol in lymphocytes from hypertensive patients.
- No significant difference in forskolin-stimulated cAMP accumulation, suggesting intact adenylyl cyclase activity.
Conclusions:
- Lymphocytes from patients with essential hypertension exhibit reduced stimulatory nucleotide-binding regulatory protein (Gs-protein) activity.
- This Gs-protein defect in lymphocytes may reflect a similar defect in the cardiovascular system, contributing to hypertension.
- The findings highlight potential cellular signaling abnormalities in the pathogenesis of essential hypertension.
Abstract:
Lymphocytes are widely used as a model for the cardiovascular beta-adrenoceptor-adenylate cyclase system. We evaluated the role of this system in the pathogenesis of hypertension by studying lymphocytes obtained from patients with essential hypertension. Untreated hypertensive patients and normotensive control subjects were studied. The number and affinity of the beta-adrenoceptors were measured by a radioligand binding method with 125I-cyanopindolol. The responses of cyclic adenosine monophosphate (cAMP) to isoproterenol, cholera toxin, and forskolin were also determined. The concentration and affinity of beta-adrenoceptors did not differ significantly in the two groups, nor was a significant difference found in the basal level of cAMP. The effects of isoproterenol on the accumulation of cAMP were reduced in the lymphocytes from the hypertensive compared with the normotensive subjects. There was no significant difference in the effect of forskolin on cAMP accumulation in the two groups. These results indicate that the activity of the stimulatory nucleotide binding regulatory protein (Gs-protein) is reduced in lymphocytes from patients with essential hypertension. This defect of Gs-protein in the lymphocytes may represent a defect of Gs-protein in the cardiovascular system in such patients.