Atrial natriuretic peptide and brain natriuretic peptide changes after epicardial percutaneous left atrial appendage suture ligation using LARIAT device.

Percutaneous left atrial appendage closure is an alternative treatment for stroke and systemic thromboembolism risk reduction in non-valvular atrial fibrillation (AF). However, the neurohormonal impact of epicardial exclusion of the left atrial appendage (LAA) with the LARIAT procedure is unknown. Evaluation of changes in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in AF patients underwent percutaneous LAA suture ligation. Sixty six patients underwent successfully percutaneous LAA suture ligation using LARIAT device. The level of ANP and BNP was measured before and 3 months after procedure. Mean ANP level before procedure was 249 ± 77 pg/mL (range from 95 pg/mL to 503 pg/mL) and mean BNP level was 481 ± 517 pg/mL (range from 34 pg/mL to 2508 pg/mL). Three months after procedure mean ANP level was 249 ± 79 pg/mL (range from 98 pg/mL to 492 pg/mL) and mean BNP level was 495 ± 526 pg/mL (range from 52 pg/mL to 2420 pg/mL). At 3 months follow up after percutaneous LAA suture ligation there were no significant differences in ANP and BNP levels.

1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway.

BACKGROUND AND PURPOSE: 1-methylnicotinamide (MNA) has been considered to be an inactive metabolite of nicotinamide. Here we assessed the anti-thrombotic activity of MNA in vivo. EXPERIMENTAL APPROACH: Antithrombotic action of MNA was studied in normotensive rats with extracorporeal thrombus formation (thrombolysis), in renovascular hypertensive rats with intraarterial thrombus formation (arterial thrombosis) and in a venous thrombosis model in rats (venous thrombosis). KEY RESULTS: MNA (3-100 mg kg(-1)) induced a dose-dependent and sustained thrombolytic response, associated with a rise in 6-keto-PGF(1alpha) in blood. Various compounds structurally related to MNA were either inactive or weaker thrombolytics. Rofecoxib (0.01-1 mg kg(-1)), dose-dependently inhibited the thrombolytic response of MNA, indomethacin (5 mg kg(-1)) abolished it, while L-NAME (5 mg kg(-1)) were without effect. MNA (3-30 mg kg(-1)) also reduced arterial thrombosis and this effect was abrogated by indomethacin (2.5 mg kg(-1)) as well as by rofecoxib (1 mg kg(-1)). MNA, however, did not affect venous thrombosis. In vitro MNA did not modify platelet aggregation nor induce vasodilation. CONCLUSIONS AND IMPLICATIONS: MNA displayed a profile of anti-thrombotic activity in vivo that surpasses that of closely related compounds. MNA inhibited platelet-dependent thrombosis by a mechanism involving cyclooxygenase-2 and prostacyclin. Our findings suggest that endogenous MNA, produced in the liver by nicotinamide N-methyltransferase, could be an endogenous activator of prostacyclin production and thus may regulate thrombotic as well as inflammatory processes in the cardiovascular system.

Hypercholesterolemia does not alter endothelial function in spontaneously hypertensive rats.

In humans, hypercholesterolemia and hypertension are associated with endothelial dysfunction. Here, we assess whether hypercholesterolemia induces endothelial dysfunction in rats with pre-existing hypertension. Spontaneously hypertensive rats (SHR) and normotensive controls (WKY) were fed with a high-cholesterol diet for 12 weeks, and endothelial function was assessed in isolated thoracic aortic rings. In SHR and WKY rats, the hypercholesterolemic diet resulted in the elevation of total cholesterol and low-density lipoprotein levels by approximately 2.5- and 4.5-fold, respectively. However, in aorta, the basal nitric oxide (NO) production--as assessed by the magnitude of L-NG-nitroarginine methyl ester-induced vasoconstriction as well as the NO-dependent relaxation induced by acetylcholine or histamine--were not diminished either in SHR or in WKY rats fed with the hypercholesterolemic diet. Interestingly, prostacyclin (PGI2) production in aortic rings from SHR rats was higher than in the aorta from WKY rats. However, the hypercholesterolemic diet had no further effects on PGI2 production in the aorta either of SHR or WKY rats. The monocyte chemoattractant protein 1 level in plasma was slightly elevated in SHR and WKY rats fed with the hypercholesterolemic diet compared with their normocholesterolemic counterparts. In summary, even in the presence of pre-existing hypertension, hypercholesterolemia fails to modify NO-dependent and PGI2-dependent endothelial function in SHR rats; it also does not induce a robust inflammatory response. Both are prerequisites for the development of atherosclerosis.