Mathar, Ilka and Vennekens, Rudi and Meissner, Marcel and Kees, Frieder and Van der Mieren, Gerry and Londono, Juan E. Camacho and Uhl, Sebastian and Voets, Thomas and Hummel, Bjoern and van den Bergh, An and Herijgers, Paul and Nilius, Bernd and Flockerzi, Veit and Schweda, Frank and Freichel, Marc (2010) Increased catecholamine secretion contributes to hypertension in TRPM4-deficient mice. JOURNAL OF CLINICAL INVESTIGATION, 120 (9). pp. 3267-3279. ISSN 0021-9738, 1558-8238
Full text not available from this repository. (Request a copy)Abstract
Hypertension is an underlying risk factor for cardiovascular disease. Despite this, its pathogenesis remains unknown in most cases. Recently, the transient receptor potential (TRP) channel family was associated with the development of several cardiovascular diseases linked to hypertension. The melastatin TRP channels TRPM4 and TRPM5 have distinct properties within the TRP channel family: they form nonselective cation channels activated by intracellular calcium ions. Here we report the identification of TRPM4 proteins in endothelial cells, heart, kidney, and chromaffin cells from the adrenal gland, suggesting that they have a role in the cardiovascular system. Consistent with this hypothesis, Trpm4 gene deletion in mice altered long-term regulation of blood pressure toward hypertensive levels. No changes in locomotor activity, renin-angiotensin system function, electrolyte and fluid balance, vascular contractility, and cardiac contractility under basal conditions were observed. By contrast, inhibition of ganglionic transmission with either hexamethonium or prazosin abolished the difference in blood pressure between Trpm4(-/-) and wild-type mice. Strikingly, plasma epinephrine concentration as well as urinary excretion of catecholamine metabolites were substantially elevated in Trpm4(-/-) mice. In freshly isolated chromaffin cells, lack of TRPM4 was shown to cause markedly more acetylcholine-induced exocytotic release events, while neither cytosolic calcium concentration, size, nor density of vesicles were different. We therefore conclude that TRPM4 proteins limit catecholamine release from chromaffin cells and that this contributes to increased sympathetic tone and hypertension.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NONSELECTIVE CATION CHANNEL; BLOOD-PRESSURE; CEREBRAL-ARTERIES; MYOGENIC RESPONSE; RENIN SECRETION; TRP CHANNELS; IN-VITRO; RECEPTOR; CELLS; ENDOTHELIUM; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 615 Pharmacy |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Frieder Kees |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2020 05:44 |
| Last Modified: | 15 Jul 2020 05:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24251 |
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