Effect of renin-angiotensin inhibition on glomerular injuries in DOCA-salt hypertensive rats

• Published in: Regulatory peptides Vol. 62; no. 2; pp. 89 - 95
• Main Authors: Oishi, Tetsuya, Ogura, Toshio, Yamauchi, Takayoshi, Harada, Kazushi, Ota, Zensuke
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 23.04.1996; Amsterdam Elsevier
• Subjects: Administration, Oral; Angiotensin I-converting enzyme inhibitor; Angiotensin II - antagonists & inhibitors; Angiotensin II receptor antagonist; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Animals; Antihypertensive Agents - administration & dosage; Biological and medical sciences; Cell Division - drug effects; Cilazapril - administration & dosage; DOCA-salt hypertensive rat; Gene Expression Regulation - drug effects; Glomerulonephritis; Glomerulus; Growth factor; Hypertension, Renovascular - metabolism; Hypertension, Renovascular - pathology; Imidazoles - administration & dosage; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Male; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Platelet-Derived Growth Factor - biosynthesis; Rats; Rats, Wistar; Receptors, Angiotensin - biosynthesis; Renin - antagonists & inhibitors; RNA, Messenger - biosynthesis; Tetrazoles - administration & dosage; Transforming Growth Factor beta - biosynthesis; Glomerulus; Angiotensin II receptor antagonist; DOCA-salt hypertensive rat; Angiotensin I-converting enzyme inhibitor; Growth factor; Renal glomerulus; Glomerulonephritis; Vertebrata; Renin angiotensin system; Urinary system disease; Mammalia; Rat; Animal; Rodentia; Renal disease; Gene expression
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/0167-0115(95)00166-2

To determine whether growth factors in the glomerulus are induced in the renin-suppressed hypertensive model, we examined the mRNA expressions of platelet-derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-β1 and angiotensin II type 1 (AT1) receptors in the glomeruli of deoxycorticosterone acetate (DOCA)-salt-treated hypertensive rats (DOCA-treated rats). We also examined the effects of treatment with cilazapril, an angiotensin I-converting enzyme inhibitor (ACEI), and L-158,809, an AT1 receptor antagonist, on these expressions in DOCA-treated rats. We administered oral 10 mg/kg of cilazapril (CILAZA group) and 1 mg/kg of L-158,809 (L158 group) to DOCA-treated rats daily. Systolic blood pressure in the two groups was not decreased compared with that in DOCA-treated rats given saline. The mRNA expressions were examined using reverse transcriptase polymerase chain reaction (RT-PCR) methods. The mRNA expressions of these genes were higher in DOCA-treated rats than in age-matched control rats. After treatment with these agents for 4 weeks, the mRNA expressions of growth factors were suppressed in both the CILAZA and L158 groups. Mesangial expansion and cell proliferation observed in DOCA-treated rats were suppressed in both the CILAZA and L158 groups. Decreases in the size of the glomerulus were observed only in the CILAZA group. These findings suggested that suppression of growth factors and glomerular proliferative changes of these agents are mediated by blocking tissue renin-angiotensin system (RAS) in the renin-suppressed model.