Phosphatidylinositol metabolism in hypertrophic rat heart.
The accumulation of inositol 1,4,5-trisphosphate (IP3) after hormonal stimulation has a physiological role, possibly by alteration of Ca2+ levels in cardiac myocyte. However, this accumulation has not been studied under pathophysiological conditions. In this report, we examine phosphatidylinositol metabolism during cellular response to norepinephrine in pressure-overloaded hypertrophic rat heart. After stimulation with norepinephrine, the accumulations of IP3 and diacylglyceride significantly increased in isolated myocytes from stroke-prone spontaneously hypertensive rat (SHRSP) heart, indicating phosphatidylinositol-specific phospholipase C activity increased in SHRSP heart cells. Protein kinase C activity was also enhanced in SHRSP, with a marked increase in particulate activity. We determined the intracellular calcium concentration and found it to be higher in SHRSP than in Wistar-Kyoto (WKY) rats at 30-40 weeks of age. Ca2+ influx was also elevated in SHRSP stimulated by norepinephrine. In SHRSP heart, cytosolic Ca2+ concentration may rise quickly in response to some stimuli, such as alpha 1-adrenergic stimulation, which is shown to be one of the pathways that increases cytosolic Ca2+ levels in hypertrophied rat heart. These data suggest that a part of the phosphatidylinositol-turnover pathway, such as the phosphatidylinositol 4,5-bisphosphate-IP3-Ca2+ pathway or the diacylglyceride-protein kinase C pathway, may play an important role in the development of hypertrophy in SHRSP heart.
Kawaguchi
H
H
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Sano
H
H
Iizuka
K
K
Okada
H
H
Kudo
T
T
Kageyama
K
K
Muramoto
S
S
Murakami
T
T
Okamoto
H
H
Mochizuki
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000150:complications; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D010716:Phosphatidylinositols; D002118:Calcium; D009638:Norepinephrine