There is an increasing evidence regarding the relationship between the metabolic syndrome and risks of cardiovascular diseases. Several studies have shown a link between metabolic syndrome components and endothelial dysfunction.

To further develop this scientific point and as little is known about the impact of metabolic syndrome on cardiovascular function in the spontaneously hypertensive rat (SHR), effects of long-term administration of BAY 41–2272, a soluble guanylate cyclase (GC) activator, on the cardiovascular reactivity of SHR rats with metabolic syndrome were investigated.

Twenty-four 9-week-old rats were randomly divided into 3 groups: control group, cafeteria diet fed group and cafeteria diet fed group receiving a daily oral dose of BAY 41–2272 (5mg/kg). Measurements of body weight, abdominal circumference, blood pressure and glucose tolerance test were performed. Cumulative concentration-response curves to isoprenaline (0.1nM–1μM), acetylcholine (1nM–10μM), phenylephrine (1nM–10μM) and insulin (1nM–3μM) as well as cGMP assays were determined on isolated perfused heart and thoracic aorta.

We showed that 12 weeks of cafeteria diet induced several components of the metabolic syndrome in cafeteria diet fed group. These metabolic disorders were associated with a decrease in ß-adrenoceptor-induced cardiac inotropy and coronary perfusion and an alteration of α₁-adrenergic response as well as insulin-induced vasorelaxation. However, no difference was observed in acetylcholine-mediated vasorelaxation between groups which is consistent with the cGMP assays. BAY 41-2272 improved markedly the in vivo measured parameters, the α₁-adrenergic-induced vasoconstriction and significantly restored the cardiac inotropy.

These results suggest that long-term activation of guanylate cyclase improved cardiovascular reactivity in SHR rats with an induced metabolic syndrome by modulating the GC-cGMP pathway.