Regulation of mitogenesis by kinins in arterial smooth muscle cells

Bradley S Dixon; Michael J Dennis

doi:10.1152/ajpcell.1997.273.1.C7

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Regulation of mitogenesis by kinins in arterial smooth muscle cells

Journal article

Peer reviewed

Regulation of mitogenesis by kinins in arterial smooth muscle cells

Bradley S Dixon and Michael J Dennis

The American journal of physiology, Vol.273(1 Pt 1), pp.C7-20

07/1997

DOI: 10.1152/ajpcell.1997.273.1.C7

PMID: 9252437

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Abstract

Recent evidence suggests that bradykinin (BK) plays a role in regulating neointimal formation after vascular injury. The present study examined the mechanism whereby BK regulates platelet-derived growth factor (PDGF) AB-induced mitogenesis in smooth muscle cells from rat mesenteric artery. BK, but not other activators of phosphoinositidase C (e.g., angiotensin II), inhibited PDGF-stimulated mitogenesis. The B1 receptor agonist des-Arg9-BK (DABK) was more potent than the B2 agonist BK; smaller BK fragments had no activity. In studies in which the B2 receptor antagonist HOE-140 {D-Arg0[Hyp3,beta-(2-thienyl)-Ala5,D-Tic7,Oic 8]BK} and the B1 receptor antagonist DHOE [[D-Arg0,Hyp3,beta-(2-thienyl)-Ala5,D-Tic7,Oi c8,des-Arg9]BK] were used, both receptors independently mediated inhibition of PDGF-induced mitogenesis. There was no evidence for metabolism of BK to DABK. The rank potency for activating phosphoinositidase C and increasing intracellular Ca2+ (BK > DABK) was opposite that for inhibiting mitogenesis (DABK > BK). Inhibition of cyclooxygenase did not prevent the kinin-mediated inhibition. Kinetic analysis of the cell cycle effects of kinins on PDGF-stimulated mitogenesis revealed that continuous exposure to DABK or BK was inhibitory even when added shortly before the cells initiated DNA synthesis (S phase). However, short-term exposure (5-60 min) to DABK or BK was inhibitory only when added after exposure to PDGF. These data suggest that the B1 and B2 receptors potently inhibited PDGF-stimulated mitogenesis and proliferation by activating an alternative signal transduction cascade not involving phosphoinositidase C or prostaglandins. The inhibition occurred at a point late in progression of the cell cycle from G1 to S and was dependent on the presence of kinins after exposure to PDGF.

Bradykinin - analogs & derivatives

Carotid Arteries - drug effects

Mesenteric Arteries - physiology

Rats, Wistar

Mesenteric Arteries - drug effects

Carotid Arteries - cytology

Receptor, Bradykinin B2

Receptor, Bradykinin B1

Bradykinin Receptor Antagonists

Bradykinin - pharmacology

Muscle, Smooth, Vascular - physiology

Muscle, Smooth, Vascular - drug effects

Mesenteric Arteries - cytology

Phosphoric Diester Hydrolases - metabolism

Cells, Cultured

Rats

Platelet-Derived Growth Factor - pharmacology

Muscle, Smooth, Vascular - cytology

Receptors, Bradykinin - agonists

Cell Division - drug effects

Cyclooxygenase Inhibitors - pharmacology

Animals

Mitosis - drug effects

Muscle Contraction - drug effects

Carotid Arteries - physiology

Enzyme Activation

In Vitro Techniques

Details

Title: Subtitle: Regulation of mitogenesis by kinins in arterial smooth muscle cells
Creators: Bradley S Dixon - Veterans Affairs Medical Center, Iowa City, Iowa, USA
Michael J Dennis
Resource Type: Journal article
Publication Details: The American journal of physiology, Vol.273(1 Pt 1), pp.C7-20
DOI: 10.1152/ajpcell.1997.273.1.C7
PMID: 9252437
ISSN: 0002-9513
eISSN: 2163-5773
Grant note: HL-42377 / NHLBI NIH HHS DK-25295 / NIDDK NIH HHS
Language: English
Date published: 07/1997
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984094709702771

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