Renal protective effect of TCV-116 in stroke-prone spontaneously hypertensive rats.

Abstract

We examined the effects of TCV-116, a non-peptide selective AT1 receptor antagonist, on cellular phenotype and on the expression of the transforming growth factor-beta 1 (TGF-beta 1) and extracellular matrix genes in the kidneys of stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given vehicle or TCV-116 (10 mg/kg/day) by gastric gavage for 10 weeks (from the age of 22 to 32 weeks). Renal mRNA levels were measured by Northern blot analysis. In vehicle-treated 32-week-old SHRSP, urinary albumin excretion per 24 h was about 26-fold greater than that in age-matched Wistar-Kyoto (WKY) rats, and the mRNA levels of renal TGF-beta 1, fibronectin and collagen types I and III in SHRSP were all several-fold higher than those in WKY. Immunohistochemical studies showed the prominent presence of alpha-smooth muscle actin-expressing glomerular cells in SHRSP, in contrast to their absence in WKY. Treatment of SHRSP with TCV-116 decreased urinary albumin excretion and renal mRNA levels for TGF-beta 1 and for the above-mentioned extracellular matrix components. TCV-116 prevented the phenotypic modulation of glomerular cells in SHRSP. These results suggest that AT1 receptor antagonists may have powerful renal protective effects.

• Authors: S Kim, K Ohta, A Hamaguchi, T Omura, T Yukimura, K Miura, Y Inada, T Wada, Y Ishimura, F Chatani
• Journal: Blood pressure. Supplement (Blood Press Suppl) Vol. 5 Pg. 54-6 ( 1994) ISSN: 0803-8023 [Print] Sweden
• PMID: 7889201 (Publication Type: Journal Article)

Chemical References

• Angiotensin Receptor Antagonists
• Antihypertensive Agents
• Benzimidazoles
• Biphenyl Compounds
• Prodrugs
• RNA, Messenger
• Receptors, Angiotensin
• Tetrazoles
• Transforming Growth Factor beta
• Angiotensin II
• candesartan cilexetil

Topics

• Albuminuria (urine)
• Angiotensin II (pharmacology)
• Angiotensin Receptor Antagonists
• Animals
• Antihypertensive Agents (therapeutic use)
• Benzimidazoles (therapeutic use)
• Biphenyl Compounds (therapeutic use)
• Cerebrovascular Disorders (physiopathology)
• Extracellular Matrix (genetics)
• Gene Expression (drug effects)
• Hypertension, Renal (metabolism)
• Kidney (drug effects, pathology, physiopathology)
• Kidney Glomerulus (metabolism, physiology)
• Male
• Phenotype
• Prodrugs (therapeutic use)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptors, Angiotensin (physiology)
• Sclerosis
• Tetrazoles
• Transforming Growth Factor beta (genetics)