Endocrine Abstracts (2001) 2 P53

Insulin-like growth factor acts as a Nitric-oxide-dependant vasodilator in normotensive but not hypertensive rat aortas

RW McCallum, C Hamilton, D Graham, E Jardine, JMC Connell & AF Dominiczak

Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK.

Insulin-like growth factor (IGF-1) has been postulated to function as a vasodilator via a nitric oxide (NO) pathway. IGF-1/growth hormone deficiency in humans is associated with endothelial dysfunction and increased cardiovascular mortality.

We compared the effects of IGF-1 on vascular function in control Wistar-Kyoto (WKY) (n=6) and stroke-prone spontaneously hypertensive rats characterised by endothelial dysfunction (SHRSP) (n=7).

Contractile responses to phenylephrine (PE) (10-8-10-5M) in the presence or absence of the NO synthase inhibitor L-NAME (10-4M) and relaxation to carbachol were studied in rat thoracic aortic control rings and rings incubated for 60 minutes with IGF-1. Maximal contractility to PE was attenuated in WKY rats by IGF-1 (0.6±0.1 to 1.1±0.1 ) (p<0.005). This difference was abolished after treatment with L-NAME (1.9±0.4 to 1.8±0.3) (p=0.9). However, in SHRSP rats, IGF-1 had no significant effect in the presence (1.4±0.1 to 1.7±0.1) (p=0.1) and absence of L-NAME ( 1.0±0.1 to 0.9±0.1) (p=0.6). IGF-1 did not modify responses to carbachol in WKY (79±8% to 89±8%) (p=0.4) and SHRSP rats (73±10% to 59±6%) (p=0.2).

These studies support the hypothesis that IGF-1 improves vascular function in control WKY rats through increasing NO availability but not in SHRSP rats and this may be important in patients with IGF-1/growth hormone deficiency.

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