Alterations in Receptor-Mediated Activation of Phospholipase A2 in DAHL Salt-Sensitive Rats

Yoshio Uehara; Satoru Takada; Yukari Kawabata; Nobuhito Hirawa; Junichi Iwai; Shuntaro Hara; Ichiro Kudo; Keizo Inoue; Masao Omata

doi:10.1291/hypres.16.105

Alterations in Receptor-Mediated Activation of Phospholipase A₂ in DAHL Salt-Sensitive Rats

Yoshio Uehara, Satoru Takada, Yukari Kawabata, Nobuhito Hirawa, Junichi Iwai, Shuntaro Hara, Ichiro Kudo, Keizo Inoue, Masao Omata

Author information

Yoshio Uehara
2nd Department of Medicine, University of Tokyo
Satoru Takada
Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine
Yukari Kawabata
2nd Department of Medicine, University of Tokyo
Nobuhito Hirawa
Kantou-Teishin Hospital
Junichi Iwai
Brookhaven National Laboratory
Shuntaro Hara
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo
Ichiro Kudo
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo
Keizo Inoue
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo
Masao Omata
2nd Department of Medicine, University of Tokyo

Keywords: Dahl salt-sensitive rats, smooth muscle cell, phospholipase A₂, phosphoinositide metabolism, phospholipase C

JOURNAL FREE ACCESS

1993 Volume 16 Issue 2 Pages 105-111

DOI https://doi.org/10.1291/hypres.16.105

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Abstract

In this study, the subcellular mechanism of impaired prostacyclin (PGI₂) synthesis in the vascular system of Dahl salt-sensitive (Dahl S) rats was investigated. Arachidonate liberation in response to PDGF or bradykinin was decreased in cultured aortic smooth muscle cell (VSMC) from Dahl S rats, compared with Dahl salt-resistant (Dahl R) rats. Phospholipase C (PIP₂-PLC) activity was lowered and the inositol 1, 4, 5-triphosphate content was also decreased in the VSMC from Dahl S rats. In fact, cytosolic calcium levels in basal and angiotensin-II stimulated conditions were significantly decreased in VSMC from Dahl S rats, compared with those in Dahl rats. There was no difference, however, in phospholipase A₂ (PLA₂) activity in the two strains. Moreover, the PLA₂ enzyme properties, e.g., its Ca²⁺ requirement, pH profile, K_m value and V_max, were equal in Dahl S and Dahl R rats. The level of functional PLA₂ messenger RNA was found to be greater in the VSMC from Dahl S rats. Similarly, PGI₂ synthesis was reduced in Dahl S rats and this was associated with an unaltered PLA₂ concentration and decreased PIP₂-PLC activity in the arterial wall. Thus, these data indicate that dysfunction of receptor-mediated PLA₂ activation is responsible for altered PGI₂ synthesis in Dahl S rats. This finding is likely mediated by a decrease in phosphoinositides metabolism. (Hypertens Res 1993; 16: 105-111)

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