Inhibitory effects of beta adrenoceptor antagonist, atenolol, on the thromboxane system in the kidney of spontaneously hypertensive rats.
We attempted to investigate the alterations in the vasoconstrictor thromboxane (TXA2) system in the kidney when spontaneously hypertensive rats (SHR) were treated subchronically with atenolol, a beta 1-adrenoceptor antagonist. Atenolol treatment (30 mg/kg body weight per day for 2 weeks) reduced systolic blood pressure by 11%, being accompanied by a decrease in heart rate. This treatment strikingly decreased thromboxane content in the renal cortex by 48% (p less than 0.05), whereas the tissue content was unaltered for prostaglandin E2 (PGE2) or slightly decreased for prostacyclin (PGI2). These alterations in the eicosanoid system led to an increase in the ratio of PGE2/TXA2 and of PGI2/TXA2. Similarly, thromboxane content in the renal papilla was lowered significantly with atenolol treatment, which raised the ratio of PGE2 to TXA2. Thromboxane reduction was not observed in the aortic walls and heart. However, in the vascular walls, PGI2 synthesis was markedly stimulated with atenolol treatment, resulting in an increase in the ratio of PGI2 to TXA2. Thus, these data indicate that subchronic atenolol-treatment inhibits the thromboxane system in the kidney, thereby shifting the eicosanoid system towards a vasodilator state. These alterations contribute, in part, to the anti-hypertensive properties of atenolol in genetic hypertension.
Hirawa
N
N
2nd Department of Medicine, Yokohama City University, Kanagawa, Japan.
Uehara
Y
Y
Numabe
A
A
Ikeda
T
T
Yagi
S
S
Sugimoto
T
T
Ishii
M
M
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001262:Atenolol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D015232:Dinoprostone / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013928:Thromboxane A2 / Q000378:metabolism*
D001262:Atenolol; D013928:Thromboxane A2; D011464:Epoprostenol; D015232:Dinoprostone