title: Intravenous insulin-like growth factor-I receptor antisense treatment reduces angiotensin receptor expression and function in spontaneously hypertensive rats.
abstract: The present study investigated the effects of a functional deficit in insulin-like growth factor-I signaling via chronic intravenous administration of insulin-like growth factor-I (IGF-I) receptor antisense in the conscious spontaneously hypertensive rat cardiovascular system. Insulin-like growth factor-I receptor (IGF-IR) antisense, but not full mismatch treatment, decreased IGF-IR expression in both conductance and resistance blood vessels. Aortic IGF-IR density was reduced by 67.4 +/- 6.0% in antisense-treated spontaneously hypertensive rat (SHR) compared with untreated animals, whereas mismatch treatment had no effect (analysis of variance, n = 3, P < 0.01). Aortic and tail artery angiotensin II type 1 receptor expression was significantly reduced by IGF-IR antisense treatment, whereas angiotensin II type 2 receptor expression was unaffected by administration of antisense and mismatch oligonucleotides. IGF-I receptor antisense treatment caused a significant decrease in pressor responses to angiotensin II in comparison with full-length mismatch treatment (E(max) was reduced to 65 +/- 7 mm Hg compared with 99 +/- 6 mm Hg, p < 0.05). Likewise, a reduction in pressor responses to noradrenaline was observed in hypertensive rats treated with IGF-IR antisense compared with full mismatch-treated rats (E(max) was reduced to 60 +/- 6 mm Hg compared with 108 +/- 5 mm Hg, p < 0.01). There was no clear antisense effect on resting blood pressure and no effect at on aortic medial thickness. These results suggest that although the proliferative and vasodilator effects of IGF-I are impaired in SHR, the effects on angiotensin receptor expression remain profound.
authors.affiliation: Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, 381 Royal Pde, Parkville, VIC, Australia 3052.
authors.forename: Tien Thuy
authors.initials: TT
authors.lastname: Nguyen
authors.forename: Nga
authors.initials: N
authors.lastname: Cao
authors.forename: Jennifer Lynn
authors.initials: JL
authors.lastname: Short
authors.forename: Paul James
authors.initials: PJ
authors.lastname: White
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006973:Hypertension / Q000378:metabolism*; D007275:Injections, Intravenous; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis* / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D016375:Antisense Elements (Genetics); D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D017526:Receptor, IGF Type 1; D009638:Norepinephrine