cyclic-gmp and Aortic-Valve-Insufficiency

Patients with aortic stenosis (AS) exhibit increased platelet aggregability, and thrombus formation has been documented on calcific and severely stenosed valves. Isolated porcine and canine aortic valves (AV) release nitric oxide (NO) and prostacyclin, which exert local antithrombotic effects; to date, this has not been studied in humans. In the present study the possible interaction of AV tissue with platelet aggregation was examined, using fragments of AV obtained from patients with AS and aortic regurgitation (AR).. Fragments of AV tissue, excised from patients undergoing AV replacement, were co-incubated with blood samples obtained from normal subjects. The direct effects of valve tissue from patients with AS (n = 14) or with predominant AR (n = 13) on ADP-induced platelet aggregation and intraplatelet cGMP and cAMP content were compared.. In whole blood, non-calcified AV fragments from AR patients inhibited platelet aggregation by 57 +/- 6% (p < 0.01); in platelet-rich plasma results were analogous. In order to determine whether this anti-aggregatory effect could be attributed to the valvular release of NO or prostacyclin, intraplatelet cGMP and cAMP formation was assessed, respectively. While there were no significant changes in cGMP content, cAMP increased by 26 +/- 4% (p < 0.02). Both, anti-aggregatory and cAMP-stimulating effects were similar to those produced by 10 nM prostaglandin E1, a prostacyclin mimetic. Fragments from stenotic valves did not inhibit aggregation and did not affect cGMP or cAMP. Furthermore, fragments from heavily calcified regions potentiated aggregation and, in some cases, induced spontaneous aggregation.. Minimally calcified aortic valves (i.e., AR) and, therefore, presumably also normal valves, exert anti-aggregatory effects, most likely via prostacyclin release. AS is associated with a loss of this effect, thus potentially contributing to thrombotic risk.

Topics: Adenosine Diphosphate; Aged; Alprostadil; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Blood Platelets; Cyclic AMP; Cyclic GMP; Dose-Response Relationship, Drug; Endothelium, Vascular; Epoprostenol; Female; Humans; Male; Middle Aged; Nitric Oxide; Platelet Aggregation; Platelet Aggregation Inhibitors; Research Design

The aim of this study was to assess the blood pressure profile and vasoactive hormones in valvular aortic disease. Thirteen aortic stenosis and/or aortic regurgitation patients were matched with 13 control subjects. Ambulatory blood pressure monitoring was performed for 24 h. Arterial and venous plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide, immunoreactive endothelin and cyclic-GMP were measured. The mean 24-h blood pressure was higher in the patient group (94.9 mmHg) compared with control subjects (88.2 mmHg) (p < 0.0001), despite no differences in daytime blood pressures. The nocturnal blood pressure fall was attenuated in the patients (systolic/diastolic blood pressure -8.5/-3.5; -20.3/-14.3 mmHg (p < 0.001/p < 0.01)); in heart rate too the nightly fall was blunted in the patients (-4.8/ -13.4/min (p < 0.0013)). PRA, Ang II, AVP, ANP, ir-ET and cGMP were significantly increased in the patients compared to the controls. Nightly systolic blood pressure fall was inversely related to arterial (r = -0.75, p < 0.003) and venous (r = -0.65, p < 0.04) plasma renin activity and arterial aldosterone (r = -0.64, p < 0.05) in valvular aortic disease patients. In conclusion, valvular aortic disease patients have attenuated falls in blood pressure and heart rate during the night. Increased activity in the renin aldosterone system may be involved in this abnormal blood pressure regulation.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Aortic Valve Insufficiency; Aortic Valve Stenosis; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Cyclic GMP; Endothelins; Female; Heart Rate; Hormones; Humans; Male; Middle Aged; Renin