atrial-natriuretic-factor and Hyperemia

Gap junctions play a key role in maintaining the functional integrity of the vascular wall. Using carbenoxolone (CBX) as a gap junction blocker, we aimed to assess the contribution of gap junctions in the vascular wall to flow-mediated vasodilatation (FMD) in healthy adults. Percentage FMD (%FMD) and circulating vasoactive molecules/activity, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), aldosterone, cortisol, plasma renin activity (PRA), and endothelin (ET-1), were measured in 25 healthy volunteers (mean age: 30.1 ± 5.4 yr; 14 males) before and after oral administration of CBX (100 mg). %FMD decreased after ingestion of CBX (9.71 ± 3.1 vs. 3.40 ± 2.0%; P < 0.0001). The levels of ANP, BNP, cortisol, and ET-1 remained stationary, while both PRA and aldosterone decreased (P < 0.005) after CBX ingestion. Blood pressure and heart rate were minimally changed by CBX. Inhibition of gap junctional communication by CBX impairs FMD in healthy persons, suggesting that physiologically, vascular gap junctions participate in the maintenance of FMD. CBX does not induce the release of vasoconstricting molecules or enhance vasoconstriction, suggesting that inhibition of gap junctional communication by CBX underlies the impairment of FMD. Therefore, administering CBX in FMD examination can be a way to follow the effect of gap junctions on endothelial function, but further work remains to verify the specificity of CBX effect.

Topics: Administration, Oral; Adult; Aldosterone; Atrial Natriuretic Factor; Brachial Artery; Carbenoxolone; Endothelin-1; Endothelium, Vascular; Female; Gap Junctions; Humans; Hydrocortisone; Hyperemia; Linear Models; Male; Natriuretic Peptide, Brain; Regional Blood Flow; Renin; Time Factors; Ultrasonography; Vasodilation

Endothelial dysfunction is a critical intermediate phenotype in the pathogenesis of cardiovascular disease. We evaluated the relative contributions of distinct biological pathways to interindividual variation in endothelial function by relating prototype biomarkers (representing these pathways) to brachial artery vasodilator function.. We investigated the cross-sectional relations of a panel of 7 biomarkers measured at a routine examination to brachial artery vasodilator function (flow-mediated dilation [FMD] and reactive hyperemia) assessed at a subsequent examination (mean interval, 2.9 years) in 2113 Framingham Heart Study participants (mean age, 61 years; 54% women). We selected biomarkers from 4 biological domains: neurohormonal (N-terminal pro-atrial natriuretic peptide [N-ANP], B-type natriuretic peptide [BNP], renin, aldosterone), hemostatic factors (plasminogen activator inhibitor-1 [PAI-1]), inflammation (C-reactive protein [CRP]), and target organ damage (urine albumin-creatinine ratio). In age- and sex-adjusted models, several biomarkers were related to baseline brachial artery diameter (PAI-1, CRP, urine albumin-creatinine ratio), baseline mean flow (N-ANP, BNP, PAI-1, CRP, aldosterone), FMD (N-ANP, PAI-1, CRP, renin), and reactive hyperemia (BNP, PAI-1, CRP, renin, urine albumin-creatinine ratio). In multivariable analyses relating the 7 biomarkers conjointly to each vascular function measure (adjusting for known risk factors), N-ANP and renin were positively related to FMD (P=0.001 and P=0.04, respectively), and N-ANP was inversely related to baseline mean flow velocity (P=0.01). None of the other biomarkers was significantly related to the vascular function measures studied.. In our large community-based sample, a conservative strategy relating several biomarkers to vascular endothelial function identified plasma N-ANP as a key correlate of mean flow under basal conditions and of FMD in response to forearm cuff occlusion.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Brachial Artery; Cross-Sectional Studies; Endothelium, Vascular; Female; Humans; Hyperemia; Inflammation; Male; Middle Aged; Regional Blood Flow; Vasodilation

The cardiac state and the prevalence of high blood pressure (BP) were analyzed in 21 pediatric patients (mean age 5.3 +/- 5.3 years) on chronic peritoneal dialysis (CPD), the aim being to specify the impact of hypervolemia in the etiology of hypertension. C- and N-terminal atrial natriuretic peptide (ANP-C, ANP-N) were measured as possible additional markers of hypervolemia. Baseline investigations were carried out 0.2 years after initiation of PD, and repeated after 0.9 +/- 0.2 years. Fifty-two percent of the patients had high BP, and in 40% the nocturnal BP decline was decreased. Left ventricular hypertrophy was present in 45%, but the systolic and diastolic functions of the heart were not impaired. Left ventricular mass correlated significantly with the severity of hypertension and with ANP-N (r = 0.79, P < 0.01 and r = 0.66, P < 0.01, Spearman rank correlation). Significant correlations were also found between the severity of hypertension and ANP-N and ANP-C (r = 0.82, P < 0.01 and r = 0.66, P < 0.01, Spearman rank correlation). High BP and cardiac impairment were more frequent in the younger and nephrectomized patients in whom volume overload seemed to be the most-important etiological factor. Our results suggest further that an ANP-N over 3.0 nmol/l combined with hypertension is strongly indicative of volume overload in patients on PD.

Topics: Atrial Natriuretic Factor; Biomarkers; Child; Child, Preschool; Echocardiography; Heart; Humans; Hyperemia; Hypertension; Nephrectomy; Peritoneal Dialysis; Prevalence

The effects of atrial natriuretic peptide (ANP) on transmural myocardial blood flow distribution and the reactive hyperemic response in the presence and absence of flow-limiting coronary stenosis were examined in chronically instrumented conscious dogs. Ten-second coronary occlusion without subsequent flow restriction resulted in marked reactive hyperemic responses (Doppler flow probes), mean flow debt repayment was 481 +/- 55%. When the 10-second coronary occlusions were followed by a 20-second partial restriction that allowed normal preocclusion coronary inflow, the subsequent reactive hyperemia was significantly augmented, mean flow debt repayment was 938 +/- 91% (p less than 0.05). Pretreatment with ANP (3 micrograms/kg) did not alter the flow debt repayment after a 10-second occlusion without restriction (474 +/- 30%, NS) but attenuated the augmentation of reactive hyperemia resulting from the 20-second inflow restriction, flow debt repayment (613 +/- 66%, NS). Regional myocardial blood flow to the ischemic region was measured during restricted inflow after a 10-second coronary occlusion before and after ANP pretreatment. Before ANP, subendocardial flow decreased (0.54 +/- 0.04 ml/min/g) and subepicardial flow significantly increased (1.03 +/- 0.12 ml/min/g) when compared with the nonischemic zone (subendocardial, 1.03 +/- 0.09 ml/min/g; subepicardial, 0.87 +/- 0.09 ml/min/g, p less than 0.05), indicating maldistribution of the restricted inflow. The resultant subendocardial-to-subepicardial ratio in the ischemic region was significantly decreased when compared with the nonischemic region (0.56 +/- 0.03 vs. 1.18 +/- 0.04, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Coronary Circulation; Coronary Disease; Dogs; Drug Evaluation, Preclinical; Hyperemia; Microspheres; Time Factors; Vasodilation; Wakefulness