Myocardial stretch stimulates phosphatidylinositol turnover.
The mammalian myocardium responds to stretch by increasing both contractility and the release of atrial natriuretic peptide. These effects are observed in isolated perfused heart preparations as well as in vivo. That atrial natriuretic peptide release can be stimulated by activation of the phosphatidylinositol turnover pathway suggests a possible mechanism by which stretch might activate a biological response. Accordingly, experiments were performed to examine the effect of dilatation of the right atrium on the phosphatidylinositol turnover pathway measured in isolated perfused hearts. Dilatation of the right atrium caused a stimulation of the phosphatidylinositol turnover pathway as measured by an increase in the accumulation of inositol phosphates. In right atria, increases were detected after 1 minute of dilatation, and maximal increases were observed after 10 minutes. Dilatation for 10 minutes caused an increase in inositol monophosphate, inositol bisphosphate, and inositol trisphosphate from 23.3 +/- 0.9, 15.4 +/- 0.4, and 9.5 +/- 0.3 cpm/mg tissue (mean +/- SEM, n = 7) to 74.6 +/- 2.3, 20.2 +/- 1.3, and 13.6 +/- 1.5 cpm/mg tissue (n = 8), respectively (p less than 0.01 for all inositol phosphates). Smaller increases were observed in the other chambers of the hearts. Perfusion with propranolol, prazosin, and atropine (all 1 microM) did not alter the inositol phosphate response to dilatation, indicating that it was not secondary to release of norepinephrine or acetylcholine. Dilatation of the right ventricle also caused a stimulation of inositol phosphate accumulation, but this was lower than after dilatation of the right atrium. These results show that the myocardium can respond to dilatation by an activation of the phosphatidylinositol turnover pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
von Harsdorf
R
R
Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
Lang
R E
RE
Fullerton
M
M
Woodcock
E A
EA
D000818:Animals; D004106:Dilatation; D006325:Heart Atria; D006352:Heart Ventricles; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010477:Perfusion; D010716:Phosphatidylinositols / Q000378:metabolism*; D010812:Physical Stimulation; D051381:Rats; D011919:Rats, Inbred Strains; D013565:Sympatholytics / Q000494:pharmacology
D010276:Parasympatholytics; D010716:Phosphatidylinositols; D013565:Sympatholytics; D009638:Norepinephrine