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(Hypertension. 1997;29:350.)
© 1997 American Heart Association, Inc.

Arthur C. Corcoran Memorial Lecture

Dopamine D1-Like Receptor Stimulation Inhibits Hypertrophy Induced by Platelet-Derived Growth Factor in Cultured Rat Renal Vascular Smooth Muscle Cells

Kenichi Yasunari; Masakazu Kohno; Hiroaki Kano; Koji Yokokawa; Mieko Minami; Junichi Yoshikawa

From the First Department of Internal Medicine, Osaka City (Japan) University Medical School.

Correspondence to Kenichi Yasunari, MD, Division of Hypertension and Atherosclerosis, First Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abenoku, Osaka 545, Japan

Vascular smooth muscle cell (VSMC) hypertrophy is believed to play some roles in atherosclerosis. To elucidate the role of vascular D1-like receptors in VSMC hypertrophy, the effects of dopamine and specific D1-like receptor agonist SKF 38393 and YM 435 on platelet-derived growth factor (PDGF) BB-mediated VSMC hypertrophy was studied. We observed that cells stimulated by PDGF-BB 5 ng/mL showed increased VSMC hypertrophy. These effects were prevented by coincubation with dopamine, SKF 38393, and YM 435 1-10 µmol/L, and this prevention was reversed by Sch 23390 1 to 10 µmol/L, a specific D1-like receptor antagonist. These actions are mimicked by forskolin 1 to 10 µmol/L, a direct activator of adenylate cyclase and 8-bromo-cAMP 0.1 to 1 mmol/L, and are blocked by a specific protein kinase A (PKA) inhibitor N-[2-(P-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H 89) but not blocked by its negative control. PDGF-BB (5 ng/mL)-mediated mitogen-activated protein kinase (MAPK) activity was significantly suppressed by coincubation with D1-like receptor agonists, which were reversed by PKA inhibitor H 89. These results suggest that vascular D1-like receptor agonists inhibit hypertrophy of VSMC, possibly through PKA activation and suppression of activated MAPK activity.

Key Words: platelet-derived growth factor • dopamine • vascular smooth muscle • hypertrophy

Abbreviations: DMEM = Dulbecco's modified Eagle's medium • FCS = fetal calf serum • MAPK = mitogen-activated protein kinase • PDGF = platelet-derived growth factor • PKA = protein kinase A • TCA = trichloroacetic acid • VSMC = vascular smooth muscle cell

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