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Renal angiotensin II receptors and protein kinase C in diabetic rats: effects of insulin and ACE inhibition.
Am J Physiol Renal Physiol. 2000 Apr; 278(4):F603-12.AJ

Abstract

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.

Authors+Show Affiliations

Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Université de Montréal, Montreal, Quebec, Canada H2W 1R7. Famiri@mail.mcg.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10751221

Citation

Amiri, F, and R Garcia. "Renal Angiotensin II Receptors and Protein Kinase C in Diabetic Rats: Effects of Insulin and ACE Inhibition." American Journal of Physiology. Renal Physiology, vol. 278, no. 4, 2000, pp. F603-12.
Amiri F, Garcia R. Renal angiotensin II receptors and protein kinase C in diabetic rats: effects of insulin and ACE inhibition. Am J Physiol Renal Physiol. 2000;278(4):F603-12.
Amiri, F., & Garcia, R. (2000). Renal angiotensin II receptors and protein kinase C in diabetic rats: effects of insulin and ACE inhibition. American Journal of Physiology. Renal Physiology, 278(4), F603-12.
Amiri F, Garcia R. Renal Angiotensin II Receptors and Protein Kinase C in Diabetic Rats: Effects of Insulin and ACE Inhibition. Am J Physiol Renal Physiol. 2000;278(4):F603-12. PubMed PMID: 10751221.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renal angiotensin II receptors and protein kinase C in diabetic rats: effects of insulin and ACE inhibition. AU - Amiri,F, AU - Garcia,R, PY - 2000/4/6/pubmed PY - 2000/5/8/medline PY - 2000/4/6/entrez SP - F603 EP - 12 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 278 IS - 4 N2 - 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. SN - 1931-857X UR - https://www.unboundmedicine.com/medline/citation/10751221/Renal_angiotensin_II_receptors_and_protein_kinase_C_in_diabetic_rats:_effects_of_insulin_and_ACE_inhibition_ L2 - http://www.physiology.org/doi/full/10.1152/ajprenal.2000.278.4.F603?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -