Characterization of the acute cardiovascular effects of intravenously administered insulin-like growth factor-I in conscious Sprague-Dawley rats.
1. Insulin-like growth factor (IGF)-I has acute effects on cardiovascular function, including a well-characterized vasodilator response in isolated arteries. In addition to increasing the release of nitric oxide, IGF-I also has effects on a variety of other signalling pathways that affect vascular tone, in particular interactions with the sympathetic nervous system and the renin-angiotensin-aldosterone system. We sought to characterize the effects of intravenous IGF-I on blood pressure and on responses to noradrenaline (NA), angiotensin II, acetylcholine and dobutamine. 2. Administration of IGF-I administration caused small decreases in mean arterial pressure (5.4 +/- 1.5%) and responsiveness to the prazosin-sensitive vasoconstrictor effects of NA (a 2.1 +/- 0.6-fold increase in ED(50); n = 40; P < 0.01) and both effects were maximal at 200 microg/kg IGF-I. In addition, IGF-I significantly increased pulse pressure increases induced by low doses of dobutamine (from an increase in pulse pressure of 9.9 +/- 1.2 to 13.4 +/- 1.9 mmHg; n = 39; P < 0.05). Administration of IGF-I had no significant effect on responses to AngII or ACh. 3. Intravenous administration of IGF-I receptor antisense oligonucleotides (400 microg/kg) abolished the effects of IGF-I on NA-induced vasoconstriction (n = 11; P < 0.05), whereas administration of a mismatch oligonucleotide did not. 4. These data indicate that the maximal effects of exogenously administered IGF-I include modest direct vasodilation and inhibition of constrictor responses to NA and an increase in the effect of dobutamine on pulse pressure. The magnitude of these effects was less than what previous in vitro studies and those performed in anaesthetized animals may have indicated likely. 5. The modest magnitude of the dilator effects of IGF-I observed in conscious rats in vivo in the present study suggests that IGF-I is unlikely to be a major player in regulating vascular tone in normotensive animals.
Cao
Nga
N
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia.
Lau
Shannen
S
Nguyen
Tien Thuy
TT
White
Paul J
PJ
D000109:Acetylcholine / Q000097:blood; D000318:Adrenergic beta-Agonists / Q000097:blood / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004280:Dobutamine / Q000097:blood / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D016376:Oligonucleotides, Antisense; D000804:Angiotensin II; D004280:Dobutamine; D007334:Insulin-Like Growth Factor I; D011433:Propranolol; D000109:Acetylcholine; D009638:Norepinephrine