Soluble guanylate cyclase chronic stimulation effects on cardiovascular reactivity in cafeteria diet-induced rat model of metabolic syndrome

Metabolic syndrome is linked to an increased risk of cardiovascular complications by a mechanism involving mainly decreased nitric oxide (NO) bioavailability and impaired NO-soluble guanylate cyclase (sGC)- cyclic guanosine monophosphate (cGMP) signalling (NO-sGC-cGMP). To further develop this scientific point, study aimed investigate the effects long-term treatment with BAY 41–2272 (a sGC stimulator) on reactivity spontaneously hypertensive rats (SHR) as model metabolic syndrome. SHR were randomly divided into 3 groups: control group, cafeteria diet (CD)-fed group CD-fed treated daily (5 mg/kg) gastric gavage for 12 weeks. In vivo measurements body weight, abdominal circumference, blood pressure glucose tolerance test performed. At end feeding period, ex cumulative concentration-response curves performed isolated perfused heart (isoproterenol (0.1 nM - 1 μM)) thoracic aorta (phenylephrine (1 nM–10 μM), acetylcholine sodium nitroprusside (SNP) nM–0.1 μM)). We showed that chronic CD induced obesity, hypertriglyceridemia, intolerance exacerbated arterial hypertension in SHR. Compared decrease β-adrenoceptor-induced cardiac inotropy, coronary perfusion aortic contraction phenylephrine. While relaxing SNP unchanged. markedly prevented development intolerance, enhanced α1-adrenoceptor-induced vasoconstriction, restored inotropy vasodilation. These findings suggest may be potential novel drug preventing