In the prospective population-based Atherosclerosis Risk in Communities(ARIC) Study, we used Cox proportional hazards regression models to investigate the association in 4195 middle-aged adults of plasma HK and PK concentrations in 1993-95 (linearly and in quartiles) with incident coronary heart disease, ischemic stroke, and heart failure through 2016.
However, despite the potential therapeutic benefit of increased natriuretic peptide and bradykinin levels, neprilysin inhibitor therapy has only modest efficacy in essential hypertension and heart failure.
To assess the mechanisms of altered HF responses to Ang-(1-7), subsets of HF myocytes were pretreated to inhibit NO synthase (L-NAME), BK (HOE-140), and Mas receptor (A-779) followed with Ang-(1-7).
Interestingly, BK application in CHF rats increased cardiac systolic and diastolic volumes and further increased the elevated LVEDP, neither of which was seen in sham rats.
Second, this review explores other hormones that are augmented by sacubitril/valsartan such as bradykinin, substance P and adrenomedullin that may contribute to the efficacy of sacubitril/valsartan in HF.
Bradykinin receptors are differentially expressed in the coronary vascular endothelium of rat and human hearts during the pathogenesis of heart failure, but the mechanisms responsible for this regulation have remained vague.
In experimental animals, bradykinin type-1 receptors (BK-1Rs) are induced during inflammation and ischemia, and, by exerting either cardioprotective or cardiotoxic effects, they may contribute to the pathogenesis of heart failure.
The regulation of the cardiac neutral endopeptidase (EC 24.10, NEP) that degrades bradykinin and natriuretic peptides has been investigated in human cardiac hypertrophy and heart failure.
Pharmacological strategies effecting more complete inhibition of serum and tissue ACE and/or potentiation of bradykinin may improve exercise capacity in patients with CHF and ACE DD genotype.