Stimulating effects of atenolol on vasodepressor prostaglandin generation in spontaneously hypertensive rats.
1. To assess the role of the vasodepressor prostaglandin system in the antihypertensive properties of beta-adrenoceptor antagonist, we investigated the alterations of prostaglandin generation in the kidney and in the aorta when spontaneously hypertensive rats were treated with atenolol for 2 weeks. 2. The blood pressure reduction was associated with an increase in urinary sodium excretion and urinary prostaglandin E2 excretion. The sodium excretion was positively related to the prostaglandin E2 excretion. 3. Basal release of prostaglandin E2 from the sliced renal cortex was enhanced by the atenolol treatment. Prostacyclin-generating capacity in the aortic wall was also significantly increased. 4. Atenolol treatment stimulated prostaglandin synthesis in the kidney and vascular wall in a dose-dependent manner. However, atenolol per se did not directly stimulate prostaglandin synthesis in the vascular wall. 5. Inhibition of prostaglandin generation by a cyclooxygenase inhibitor, indomethacin, was associated with attenuation of the antihypertensive effects of atenolol. 6. Thus these data indicate that sub-chronic atenolol treatment stimulates vasodepressor prostaglandin generation in the kidney and in the aortic vessels, and this shares the antihypertensive effects of this drug with the mechanism of beta-adrenergic antagonism probably mediated through vasorelaxation and natriuresis.
Hirawa
N
N
2nd Department of Internal Medicine, Yokohama City University, Japan.
Uehara
Y
Y
Numabe
A
A
Takada
S
S
Matsuoka
H
H
Ikeda
T
T
Sugimoto
T
T
Yagi
S
S
Ishii
M
M
D000818:Animals; D001262:Atenolol / Q000627:therapeutic use*; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects*
D011453:Prostaglandins; D001262:Atenolol; D012964:Sodium; D015232:Dinoprostone; D007213:Indomethacin