It is well known that systemic
insulin resistance is closely associated with the
metabolic syndrome including
type 2 diabetes and
hypertension. However, it remains unclear whether vascular
insulin resistance acts as an early etiologic factor for the development of
hypertension. Male spontaneously hypertensive rats (SHRs) aged 5 weeks (young) and 15 weeks (adult) were studied and vascular
insulin resistance was assessed as the function of isolated aortic vasodilatory response to
insulin in vitro. Compared with Wistar-Kyoto (WKY) rats, adult SHRs exhibited significant
hypertension with significantly decreased aortic vasodilatation to
insulin, whereas young SHRs had normal blood pressure but exhibited similar vascular
insulin resistance. Both young and adult SHRs showed significant downregulated expression of
PI3-kinase and decreased
insulin-stimulated phosphorylations of Akt and eNOS in vascular tissues. Treatment with
rosiglitazone (RSG), an
insulin sensitizer, for 2 weeks increased vascular
PPARgamma expression and restored
PI3-kinase/Akt/eNOS-mediated signaling pathway only in young SHRs. More importantly, this treatment improved aortic vasodilatory response to
insulin in young but not in adult SHRs. In summary, vascular
insulin resistance, characterized by the impairment of
PI3-kinase/Akt/eNOS-mediated signaling in vascular endothelium, may play important roles in endothelial dysfunction and subsequent development of
hypertension in normotensive young SHRs.