Rescue of pulmonary hypertension with an oral sulfonamide antibiotic sulfisoxazole by endothelin receptor antagonistic actions.
Pulmonary hypertension (PH) is a disease of unknown etiology that ultimately causes right ventricle heart failure with a lethal outcome. An increase in circulating endothelin (ET)-1 levels may contribute to disease progression. This study aimed to examine the possible effects of an orally active ET receptor antagonist, sulfisoxazole (SFX), for the rescue of PH, right ventricular hypertrophy, and eventual right ventricular failure. PH rats (single injection of monocrotaline [MCT]) were treated with an ET antagonist, SFX, an orally active sulfonamide antibody. Effects of SFX on PH rats were assessed in terms of survival rate, pulmonary artery blood pressure (PABP), autonomic nerve activity, and atrial natriuretic peptide (ANP) concentration in right ventricular myocytes and plasma. SFX did not change systemic blood pressure, however, it significantly suppressed the elevation of PABP. SFX maintained the derangement of autonomic nerve control, blunted an increase in ANP in myocytes and plasma, and significantly improved survival in right heart failure and/or related organs dysfunction in PH rats. The ET antagonistic action of the antimicrobial agent, SFX, was experimentally confirmed for treatment of PH in rats.
Uchino
Tomoko
T
Department of Cardiovascular Science, Oita University School of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Japan.
Sanyal
Shamarendra N
SN
Yamabe
Motoko
M
Kaku
Toshihiko
T
Takebayashi
Satoshi
S
Shimaoka
Toru
T
Shimada
Tatsuo
T
Noguchi
Takayuki
T
Ono
Katsushige
K
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004562:Electrocardiography; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D006339:Heart Rate; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000378:metabolism; D013444:Sulfisoxazole / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology
D000890:Anti-Infective Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D017466:Receptors, Endothelin; D013444:Sulfisoxazole; D009320:Atrial Natriuretic Factor