Kallistatin is a potent new vasodilator

Title

Kallistatin is a potent new vasodilator

Creator

Chao J L; Stallone J N; Liang Y M; Chen L M; Wang D Z; Chao L

Publisher

Journal of Clinical Investigation

Date

1997
1997-07

Description

Kallistatin is a serine proteinase inhibitor which binds to tissue kallikrein and inhibits its activity, The aim of this study is to evaluate if kallistatin has a direct effect on the vasculature and on blood pressure homeostasis. We found that an intravenous bolus injection of human kallistatin caused a rapid, potent, and transient reduction of mean arterial blood pressure in anesthetized rats. Infusion of purified kallistatin (0.07-1.42 nmoVkg) into cannulated rat jugular vein produced a 20-85 mmHg reduction of blood pressure in a dose-dependent manner. Hoe 140, a bradykinin B-2-receptor antagonist, had no effect on the hypotensive effect of kallistatin yet it abolished the blood pressure-lowering effect of kinin and kallikrein. Relaxation of isolated aortic rings by kallistatin was observed in the presence (ED50 of 3.4 x 10(-9) M) and in the absence of endothelium (ED50 of 10(-9) M). Rat kallikrein-binding protein, but not kinin or kallikrein, induced vascular relaxation of aortic rings. Neither Hoe 140 nor N-omega-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, affected vasorelaxation induced by kallistatin. Kallistatin also caused dose-dependent vasodilation of the renal vasculature in the isolated, perfused rat kidney, Specific kallistatin-binding sites were identified in rat aorta by Scatchard plot analysis with a K-d of 0.25+/-0.07 nM and maximal binding capacity of 47.9+/-10.4 fmol/mg protein (mean+/-SEM, n = 3). These results indicate that kallistatin is a potent vasodilator which may function directly through a vascular smooth muscle mechanism independent of an endothelial bradykinin receptor. This study introduces the potential significance of kallistatin in directly regulating blood pressure to reduce hypertension.

Subject

Research & Experimental Medicine; expression; purification; endothelium; vasopressin; inhibitor; bradykinin; blood pressure; human tissue kallikrein; hypertensive rats; kallikrein; kallikrein-binding protein; kallistatin; kinins; renal pressure; vasorelaxation

Identifier

Format

Journal Article or Conference Abstract Publication

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

11-17

Issue

1

Volume

100

Citation

Chao J L; Stallone J N; Liang Y M; Chen L M; Wang D Z; Chao L, “Kallistatin is a potent new vasodilator,” NEOMED Bibliography Database, accessed September 23, 2021, https://neomed.omeka.net/items/show/8856.

Social Bookmarking