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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
ENDOTHELIN-1 ALTERS CALCIUM TRANSIENTS IN ATRIAL MYOCYTES FROM SPONTANEOUSLY HYPERTENSIVE RATS
Abstract number: P017
Pluteanu1 *F., Kiess1 T., Sack1 C., Nikonova1 Y., Plackic1 J., Roderick2 H.L., Kockskamper1 J.
1Philipps-Universitt Marburg, Pharmakologie und Klinische Pharmazie, Marburg, Germany
2Babraham Institute, Laboratory of Molecular Signalling, Cambridge, United Kingdom
Question:
Chronic hypertension induces left ventricular hypertrophy and, moreover, is a major risk factor for the development of atrial fibrillation. Previous studies have shown that IP3-dependent Ca signaling is altered in the left ventricle of hearts with hypertension-induced hypertrophy. However, the role of IP3-dependent Ca signaling in atria of hypertensive animals is not known to date. Thus, we tested whether IP3-dependent atrial Ca signaling is altered during hypertension-induced left ventricular hypertrophy.
Methodology:
Six to eight months old spontaneously hypertensive rats (SHR) were compared to age-matched Wistar-Kyoto rats (WKY) serving as controls. Epifluorescence (Fura-2/AM) and sarcomere length detection were used to quantify global [Ca] transients (CaTs) and contraction in electrically stimulated (1 Hz at RT) atrial myocytes. Endothelin-1 (ET-1, 50nM) was used to stimulate IP3 signaling. Protein expression of IP3 receptor type 2 (IP3R2) was measured in left atrial tissue by Western Blotting.
Results:
At 68 months of age, SHR exhibited compensated left ventricular hypertrophy. Atrial size (weight) was decreased in SHR. In both WKY and SHR ~80% of atrial myocytes responded to ET-1 with a biphasic response. CaTs and fractional shortening decreased in the first 35 min in a similar way in both groups (by ~20% and ~55%, respectively), followed by an increase that reached the maximum after ~20 min. The magnitude of the ET-1-induced increase of the CaT amplitude was larger in SHR (192.8±34.7%, n=7) than in WKY (129.6±9.7%, n=13, P<0.05), while the corresponding increase in fractional shortening was comparable. Western blot analysis indicated that expression of IP3R2 in the left atrium was decreased in SHR (WKY: 1.38±0.14, n=5 vs SHR: 0.85±0.1, n=5, P<0.05).
Conclusion:
Our results show that, in atrial myocytes from 68 months old SHR with compensated left ventricular hypertrophy, ET-1 induced complex alterations in electrically stimulated CaTs and contraction. The pronounced late increase in CaTs - presumably mediated in part by IP3-dependent Ca release - occurred despite a reduction in the expression of IP3R2.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :P017