[The effects of endothelin blockade on renal expression of angiotensin II type 1 receptor in diabetic hypertensive rats].
OBJECTIVE
To investigate the changes of angiotensin II type 1 (AT1) receptor in the kidney of spontaneously hypertensive rats (SHR) with diabetes and the influence of endothelin receptor antagonist bosentan.


METHODS
Streptozotocin-induced diabetic SHR were divided into four groups: groups treated by cilazapril, bosentan + amlodipine, and amlodipine rsspectively, and untreated group, 6 rats in each group. Six SHR rats and six WKY rats were used as hypertensive and normotensive controls respectively. By the end of the 4th week, all rats were anasthetized and catheteization was conducted to their right common carotis arteries to measure the mean arterial blood pressure and collect blood samples to determine the blood sugar and creatinine by biochemical analyzer, and plasma angiotensin II level by radioimmunoassay. Then the rats were killed and their kidneys were taken. The renal angiotensin II (Ang II) receptor and expression of AT1 receptor was determined by RT-PCR and Western blotting. One day before the rats were killed, 24-hour urine was collected to determine the urinary protein and creatinine.


RESULTS
In untreated diabetic SHR, enhanced blood pressure and urinary protein excretion, reduced creatinine clearance, as well as significantly increased plasma and renal Ang II levels were observed compared with those in WKY rats. Immunohistochemistry, Western blotting and semi-quantitatively RT-PCR methods showed that the protein and mRNA levels of AT1 receptor in kidney were significantly reduced in untreated diabetic SHR compared to those in WKY rats. All these abnormalities were attenuated by bosentan + amlodipine and cilazapril therapies.


CONCLUSIONS
Bosentan prevents the down-regulation of AT1 receptor in the kidneys of diabetic hypertensive rats.
Gu
Yong
Y
Department of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Chen
Jing
J
Yang
Haichun
H
Zhu
Weiyu
W
Lin
Fan
F
Zhu
Chunxiao
C
Lin
Shantan
S
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077300:Bosentan; D017315:Cilazapril / Q000494:pharmacology / Q000627:therapeutic use; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013449:Sulfonamides; D017315:Cilazapril; D017311:Amlodipine; D000077300:Bosentan