Application of monoclonal antibodies for endothelin to hypertensive research

Yoshihiko Saito, Kazuwa Nakao, Masashi Mukoyama, Gotaro Shirakami, Hiroshi Itoh, Takayuki Yamada, Hiroshi Arai, Kiminori Hosoda, Shin Ichi Suga, Michihisa Jougasaki, Yoshihiro Ogawa, Shigeyuki Nakajima, Motohiko Ueda, Hiroo Imura

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63 Citations (Scopus)

Abstract

We developed six kinds of monoclonal antibodies against endothelin (ET)-l recognizing different epitopes with high affinities (5x1010 M-1 to 5x1O11 M-1). Using these monoclonal antibodies, we developed radioimmunoassays for ET-1 with different specificities. Crossreactivities with ET-2 ranged from 80% to 100%, and those with ET-3 ranged from 3% to 60%. Patients with essential hypertension (si=20) showed a significant elevation in the plasma ET-l-LI level compared with age-matched control subjects (n = 12) (30.1 ±1.4 pg/ml versus 18.5±0.9 pg/ml, p<0.01). The plasma ET-l-LI level in hypertensive patients in stages II and 111 (World Health Organization classification) was significantly higher than that in those patients in stage I. There was no significant correlation between the plasma ET-l-LI level and systolic blood pressure (r=0.11), diastolic blood pressure (r=-0.13), or age (r=0.24) in all patients studied who had essential hypertension. In the neutralization experiment, monoclonal antibodies attenuated ET-l-induced contraction of rat aortic rings and the pressor action of ET-1 in pithed rats in vivo. The present study demonstrates the elevated plasma ET-l-LI level in patients with essential hypertension. Monoclonal antibodies developed in this study can become powerful tools to investigate the pathophysiological significance of ET in essential hypertension.

Original languageEnglish
Pages (from-to)734-738
Number of pages5
JournalHypertension
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 1990
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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