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It has been shown that glomerular ANG II receptors are downregulated and protein kinase C (PKC) activity is enhanced in diabetes mellitus. Therefore, we investigated glomerular and preglomerular vascular ANG II receptors and PKC isoform regulation in streptozotocin (STZ)-diabetic rats treated with insulin and/or captopril. Diabetic rats were prepared by injecting STZ (60 mg/kg). Those that developed diabetes after 48 h were treated with low or high doses of insulin, or with a low dose of insulin as well as captopril, and killed 14 days later. Their glomeruli and preglomerular vessels were purified, competitive binding studies were performed by using the ANG II antagonists losartan and PD-123319, and PKC analysis was carried out by Western blotting. Competitive binding studies showed that the AT(1) receptor was the only ANG II receptor detected on both glomeruli and preglomerular vessels of all groups. Preglomerular vascular AT(1) receptor density (B(max)) was significantly upregulated in low insulin-treated STZ rats, whereas glomerular AT(1) B(max) was downregulated. Furthermore, both the captopril- and high insulin-treated groups had less glomerulosclerosis and vascular damage than the low insulin-treated group. PKCalpha, PKCdelta, PKCepsilon, and PKCmu isoforms found in preglomerular vessels were upregulated by captopril and high insulin doses, respectively, whereas no such regulation occurred in glomeruli. We conclude that in STZ-diabetic rats ANG II receptors and PKC isoforms on preglomerular vessels and glomeruli are differentially regulated by treatment with insulin and/or captopril.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10751221&dopt=Abstract




Pharmacol Res. 2000 May;41(5):555-63.
Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats.

Zuhair HA, Abd El-Fattah AA, El-Sayed MI.

Pharmacology Department, Faculty of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia.

Natural products like pumpkin-seed oil (PSO) may modify the potency of the calcium antagonist felodipine (FEL) or angiotensin-converting enzyme inhibitor (ACE-inhibitor), captopril (CPT) in modulating the biochemical derangement in blood, heart and kidney as well as blood pressure and heart rate of spontaneously hypertensive rats (SHR) were investigated. SHR were treated orally with FEL at a dose of 0. 45 mg kg(-1) body wt. or CPT at a dose of 9 mg kg(-1) body wt. once daily for 4 weeks. PSO was administered at a dose of 40 mg kg(-1) body wt. alone or with FEL or CPT in the previous respective dose regimen for the same period to SHR. This study showed that hypertension induced increments the content of malondialdehyde (MDA) by 55% and 38% as well as the activity of glutathione peroxidase (GSH-Px) by 26% and 23% in heart and kidney, respectively, accompanied by reductions in the activity of myocardial superoxide dismutase (SOD) from 3.40+/-0.17 to 2.42+/-0.19 U mg protein(-1)and contents of glutathione (GSH) and protein thiols (PrSHs) in different tissues of SHR as compared to normotensive rats. Treatment of SHR with FEL or CPT monotherapy or combined with PSO produced improvement in the measured free radical scavengers in the heart and kidney. Our results also showed that pretreatment of SHR with PSO for 4 weeks then i.v. administration of FEL or CPT produced a significant beneficial hypotensive action. The results were explained in the light of the antioxidant properties of PSO. Therefore, it is concluded that concomitant administration of FEL or CPT with natural antioxidants can yield a beneficial therapeutic effect and retard the progression of hypertension. Copyright 2000 Academic Press.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10753555&dopt=Abstract




Rev Med Chir Soc Med Nat Iasi. 1999 Jul-Dec;103(3-4):140-6.
[The effects of the intraventricular administration of captopril on water and ion metabolism in the rst]

[Article in Romanian]

Slatineanu SM, Haulica I, Costuleanu A, Mandreci I, Petrescu G.

Disciplina de Fiziologie, Facultatea de Medicina, Universitatea de Medicina si Farmacie Gr. T. Popa, Iasi.

The effects of the conversion enzyme on the hydroelectrolytic balance in adult rats, maintained in standard lab conditions have been followed. The administration protocol for the conversion inhibitor (captopril) produced a blocking of the transformation of angiotensin I in angiotensin II only at the level of the cerebral structures, during the whole period of the treatment (40 micrograms/kg x 3/24 hours). Following the intracerebroventricular (ICV) administration of captopril, the fluid ingestion decreased diuresis and urinary elimination of Na+ and Ca++ increased. The results plead for the existence of a cerebral renin-angiotensin system, which intervenes in the control of the hydroelectrolyte metabolism.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10756941&dopt=Abstract












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