Vasoconstrictors and renal protection induced by beta 1-selective adrenoceptor antagonist bisoprolol.
We investigated the role of the vasoconstrictors endothelin-1 (ET-1) and thromboxane in renal protection by the beta 1-selective adrenoceptor antagonist, bisoprolol, in Dahl salt-sensitive rats (Dahl S) and salt-resistant rats (Dahl R). Six-week bisoprolol treatment (20 mg/kg chow) reduced systolic blood pressure (SBP) by 14% in Dahl S rats fed a high-salt (4% NaCl) diet. This BP reduction was accompanied by a decrease in aortic wall thickness. ET-1 and thromboxane released from renal cortex was significantly decreased by 17 and 30% with bisoprolol, respectively. Other prostaglandin synthesis was unaffected. Renal function such as proteinuria, N-acetyl-beta-D-glucosaminidase (NAG) excretion, and glomerular filtration rate (GFR) was not influenced by bisoprolol. Morphologic investigation showed that bisoprolol significantly improved glomerular sclerosis by 29% and attenuated arterial damage by 71%, although tubular injury was not affected. The more severe the glomerulosclerotic lesions, the greater the generation of thromboxane and ET. The arterial lesions were positively correlated to thromboxane generation. These data indicate that long-term bisoprolol treatment reduces vasoconstrictive ET-1 and thromboxane generation and that these alterations may be partly responsible for the amelioration of glomerular and arterial injury in Dahl S rats.
Uehara
Y
Y
2nd Department of Medicine, University of Tokyo, Japan.
Takada
S
S
Hirawa
N
N
Kawabata
Y
Y
Ohshima
N
N
Numabe
A
A
Ishimitsu
T
T
Goto
A
A
Yagi
S
S
Omata
M
M
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use* / Q000652:urine; D000818:Animals; D017298:Bisoprolol / Q000627:therapeutic use* / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D016232:Endothelins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D011188:Potassium / Q000097:blood; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects; D012964:Sodium / Q000097:blood / Q000652:urine; D012982:Sodium, Dietary / Q000009:adverse effects / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D014280:Triglycerides / Q000097:blood
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D016232:Endothelins; D018342:Receptors, Adrenergic, beta-1; D012982:Sodium, Dietary; D013931:Thromboxanes; D014280:Triglycerides; D002784:Cholesterol; D012964:Sodium; D011188:Potassium; D017298:Bisoprolol