This Article Full Text Full Text (PDF) All Versions of this Article: 45/3/419    most recent 01.HYP.0000156496.15668.62v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Izumiyama, H. Articles by Shichiri, M. Search for Related Content PubMed PubMed Citation Articles by Izumiyama, H. Articles by Shichiri, M. Related Collections Contractile function Other etiology

(Hypertension. 2005;45:419.)
© 2005 American Heart Association, Inc.

Original Articles

Synthetic Salusins as Cardiac Depressors in Rat

Hajime Izumiyama; Hiroyuki Tanaka; Koso Egi; Makoto Sunamori; Yukio Hirata; Masayoshi Shichiri

From the Tokyo Medical and Dental University Medical Hospital (H.I., M. Shichiri), Department of Clinical and Molecular Endocrinology (H.I., Y.H.), and Department of Cardio-thoracic Surgery (H.T., K.E., M. Sunamori), Tokyo Medical and Dental University, Bunkyo-ku, Japan.

Correspondence to Masayoshi Shichiri, MD, PhD, Tokyo Medical and Dental University Medical Hospital, 1–5–45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail mshichiri.cme{at}tmd.ac.jp

Abstract

Using bioinformatic analyses of full-length, enriched human cDNA libraries, we recently identified salusins, multifunctional related peptides ubiquitously expressed in major human tissues. Salusins cause transient and profound hypotension when injected intravenously to rats, the hypotensive effect of salusin-ß being especially striking. However, the mechanisms of this hypotensive action remain elusive. To determine whether salusins modulate cardiac function in rats, we studied serial changes of systemic hemodynamics and functions of isolated perfused working and nonworking hearts before and after salusin administration. Intravenous salusin-ß administration to intact anesthetized rats caused a temporary rapid, profound decrease in aortic blood flow concomitantly with hypotension and bradycardia without affecting systemic vascular resistance. Salusin-ß-induced hypotension and bradycardia were completely blocked by pretreatment with atropine, a muscarinic receptor antagonist, but not by propranolol. In isolated perfused working rat hearts, salusin-ß significantly decreased cardiac output, aortic flow, and stroke work. However, it did not affect coronary flow in isolated working and nonworking hearts. Our results indicate that salusins induce potent hypotension via negative inotropic and chronotropic actions. Salusin-ß promotes its actions by facilitating vagal outflows to the heart, whereas the negative inotropism of salusin-ß is also mediated via a direct myotropic effect.

Key Words: cardiac output • heart rate • blood pressure • vascular resistance

This article has been cited by other articles:

				T. Watanabe, K. Nishio, T. Kanome, T.-a. Matsuyama, S. Koba, T. Sakai, K. Sato, S. Hongo, K. Nose, H. Ota, et al. Impact of Salusin-{alpha} and -{beta} on Human Macrophage Foam Cell Formation and Coronary Atherosclerosis Circulation, February 5, 2008; 117(5): 638 - 648. [Abstract] [Full Text] [PDF]