Right coronary artery ligation in mice: a novel method to investigate right ventricular dysfunction and biventricular interaction

International audienc

Increased α1-adrenoreceptor activity is required to sustain blood pressure in female rats under food restriction.

Aims: Weevaluated the effect of food restriction (FR) on the various reflexes involved in short termcardiovascular regulation; we also evaluated the contribution of the sympathetic nervous systemand of the plasmatic nitric oxide (NO) in the development of the counterregulatory cardiovascular changes triggered by FR. Main methods: Female rats were subjected to FR for 14 days, and after this period biochemical measurements of biochemical parameterswere performed. For physiological tests, animalswere anaesthetised, and a catheter was inserted into the femoral artery and vein for the acquisition of blood pressure and heart hate, and drug infusion, respectively.We then tested the Bezold–Jarisch reflex, the baroreflex and chemoreflex and the effect of the infusion of adrenergic receptor antagonists in control and food restricted animals. Key findings: The rats subjected to severe FR presented biochemical changes characteristic ofmalnutrition with a great catabolic state. FR also led to hypotension and bradycardia besides reducing the plasmatic concentration of NO. Moreover, activation of the Bezold–Jarisch reflex induced a more pronounced hypotensive response in animals subjected to FR. Intravenous infusion of a α1-adrenoreceptor antagonist induced a greater hypotensive response and a more pronounced tachycardic response in animals under food restriction,while the infusion of β- adrenoreceptor antagonist induced lower increases in blood pressure in these animals. Significance: Our results suggest that an increased α1-adrenoreceptor activity in the resistance arteries coupled with a reduction of plasmatic NO contributes in a complementary manner to maintain the blood pressure levels in animals under FR

Early calcium handling imbalance in pressure overload-induced heart failure with nearly normal left ventricular ejection fraction

International audienceHeart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high morbidity and mortality. Therapeutic options are limited due to a lack of knowledge of the pathology and its evolution. We investigated the cellular phenotype and Ca2+ handling in hearts recapitulating HFpEF criteria. HFpEF was induced in a portion of male Wistar rats four weeks after abdominal aortic banding. These animals had nearly normal ejection fraction and presented elevated blood pressure, lung congestion, concentric hypertrophy, increased LV mass, wall stiffness, impaired active relaxation and passive filling of the left ventricle, enlarged left atrium, and cardiomyocyte hypertrophy. Left ventricular cell contraction was stronger and the Ca2+ transient larger. Ca2+ cycling was modified with a RyR2 mediated Ca2+ leak from the sarcoplasmic reticulum and impaired Ca2+ extrusion through the Sodium/Calcium exchanger (NCX), which promoted an increase in diastolic Ca2+. The Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2a) and NCX protein levels were unchanged. The phospholamban (PLN) to SERCA2a ratio was augmented in favor of an inhibitory effect on the SERCA2a activity. Conversely, PLN phosphorylation at the calmodulin-dependent kinase II (CaMKII)-specific site (PLN-Thr17), which promotes SERCA2A activity, was increased as well, suggesting an adaptive compensation of Ca2+ cycling. Altogether our findings show that cardiac remodeling in hearts with a HFpEF status differs from that known for heart failure with reduced ejection fraction. These data also underscore the interdependence between systolic and diastolic "adaptations" of Ca2+ cycling with complex compensative interactions between Ca2+ handling partner and regulatory proteins