Changes of brain endothelin levels and peripheral endothelin receptors by chronic cigarette smoke in spontaneously hypertensive rats.
The present study was conducted to evaluate the contribution of endothelin (ET) to the pharmacodynamic response to chronic cigarette smoke in spontaneously hypertensive rats (SHR). The contribution of ET was studied consequent to the hemodynamic response following 8 weeks of cigarette smoke by determining the changes in tissue ET-1 content and ET receptors. The blood pressure (BP) at the early phase of smoking and the heart rate (HR) 24 h later were apparently reduced in SHR, while the HR at the early phase was transiently elevated in normotensive Wistar Kyoto (WKY) rats. Tissue ET-1 levels in the hypothalamus, striatum, and cortex of SHR were higher than those in WKY rats, and these higher levels in SHR were reduced by exposure to chronic cigarette smoke. The ET-1 contents in the medulla oblongata and midbrain of both strains were clearly increased by smoke exposure, although the levels of SHR and WKY rats were not different. In addition, the immunoreactivity of the ET type A receptor in the adrenal glands and type B receptor in the kidneys of SHR showed a different response to smoke exposure as compared to WKY rats. Our present findings suggest that the changes of ETs may relate to the pharmacodynamic effects of chronic cigarette smoke.
Ohno
Norikazu
N
Department of Pharmacology, Nara Medical University, Japan.
Tanaka
Takeshi
T
Kita
Taizo
T
Kubo
Kaoru
K
Shimada
Keiji
K
Yonetani
Yukio
Y
Konishi
Noboru
N
Nakashima
Toshikatsu
T
D000313:Adrenal Medulla / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016232:Endothelins / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044022:Receptor, Endothelin A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects / Q000503:physiopathology*; D013997:Time Factors; D014026:Nicotiana / Q000009:adverse effects*
D016232:Endothelins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012906:Smoke