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Acta Physiologica 2012; Volume 205, Supplement 690
Joint Meeting of the Hungarian Biophysical Society, Hungarian Physiological Society, Hungarian Society of Anatomists and Hungarian Society of Microcirculation & Vascular Biology
6/11/2012-6/13/2012
Debrecen, Hungary
DIRECT CORONARY EFFECTS OF ACETYLCHOLINE IN ISOLATED RAT HEARTS MODULATED BY PROSTAGLANDINS
Abstract number: P8
Dezsi2 L, Kerekes1 M, Mihalyi1 Cs, Magyar3 J, Merkely1 B, Kekesi1 V
1Heart Centre, Semmelweis University, Budapest, Hungary
2Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary
3Department of Physiology, University of Debrecen, Debrecen, Hungary
Earlier we have shown that steady state coronary response to acetylcholine (ACh) in isolated rat hearts appears as the complex result of vasoconstrictor and vasorelaxing effects. It was also shown that both components were mediated by M3 muscarinic receptors. The presence of M3 receptors in the vascular wall was confirmed by specific immunostaining. Endothelial denudation or nitric oxide synthase (NOS) blockade abolished relaxation, while constriction was significantly increased by NOS inhibition. In our present studies, in the same model using constant perfusion rate and elevated coronary perfusion pressure (CPP) (by vasopressin 1 IU/L, CPP: 98±3 Hgmm) changes in the effects of ACh (0.01–0.1–1mM, infusions of 5–5 min) oncoronaries were investigated. The effects of non-specific cyclooxygenase (COX; indomethacin 5mM), or phosphodiesterase (PDE; pentoxifillin 200mM), or PDE5 isoenzyme blockers (vardenafil 250 nM) were studied. Endothelial or smooth muscle function was tested by boluses of bradykinin or sodium nitroprusside, respectively. Vascular effects of ACh were started by an initial dilation (DCPPmax: -9±1 Hgmm, n=38, p<=0.01), followed by constriction (DCPPmax: 16±2 Hgmm, n=38, p<=0.01), and terminated by late dilation (DCPPmax: -32±3 Hgmm, n=38, p<=0.01). COX blockade did not affect the relaxation phase, while constriction was slightly augmented (DCPPmax: 28±7 vs. 18±6 Hgmm, n=5, p<=0.05). PDE blockade did not affect
ACh-induced relaxation, but constriction was significantly reduced (DCPPmax: 3±8 vs. 23±3 Hgmm, n=6, p<=0.05). PDE5 blockade also failed to increase the relaxation phase, while vasoconstriction was reduced to a lesser extent compared with PDE blockade (DCPPmax: 5±3 vs. 7±4 Hgmm, n=6, p<=0.05). The slight increase in constriction in response to COX inhibition suggests the modulator role of vasorelaxing prostaglandins on the coronary effects of ACh. Different compensatory effects of
PDE/PDE5 inhibition on ACh-induced constrictor components may reflect a concerted role of cGMP and cAMP mediated pathways.
Supported by TÁMOP-4.2.2/08/1/KMR research grant.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 205, Supplement 690 :P8