Pulmonary vasorelaxant activity of atrial natriuretic peptide and brain natriuretic peptide in humans.

BACKGROUND--Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) exhibit in vitro pulmonary vasodilator activity, but little information is available regarding their effects in the human pulmonary vasculature. Their effects in the human pulmonary circulation and their ability to modulate the pulmonary pressor effects of angiotensin II have therefore been evaluated. METHODS--Eight healthy volunteers were studied on three separate occasions. Infusions of either ANP, BNP, or placebo were given for 60 minutes with a concomitant infusion of angiotensin II given for the final 30 minutes. Pulmonary haemodynamics were measured by pulsed wave Doppler echocardiography at baseline (T0), before commencing angiotensin II (T30), and at the end of the infusion period (T60). RESULTS--Mean pulmonary artery pressure (MPAP) showed a fall with ANP and BNP infusion at T30 compared with placebo. Although angiotensin II infusion had significant pulmonary pressor effects on all three study days, MPAP at T60 was lower when ANP (18.3 (2.0) mm Hg) and BNP (16.1 (1.5) mm Hg) were given concomitantly compared with placebo (21.8 (1.6) mm Hg). CONCLUSIONS--These findings indicate that both ANP and BNP exhibit pulmonary vasorelaxant activity in humans in terms of antagonism of the pulmonary pressor effects of angiotensin II. This would support the hypothesis that ANP and BNP act as circulating counter-regulatory hormones in states of pathological pulmonary vasoconstriction.     

MEASUREMENT OF NORMAL HUMAN AIRWAYS RESPONSE TO β-ADRENOCEPTOR STIMULATION USING A FORCED OSCILLATION TECHNIQUE

The purpose of the present study was to evaluate the responsiveness of normal human airways to beta-adrenoceptor stimulation using a forced oscillation technique. Seven normal volunteers (aged 25 +/- 2 year) were studied on three occasions, separated by weekly intervals, using a single-blind randomized design. On day 1, subjects were given cumulative doses of inhaled salbutamol (100, 200, 500, 1000 micrograms); and identical placebo was given on the other two visits. Respiratory oscillation impedance (Ros) was measured at baseline and 15 min after each dose increment. The coefficients of variation (CV) for short-term intra-individual variability on each placebo day were 7.5 and 9.5, and 9.6% for long-term variability (measured over all three visits). The 95% confidence values (2SD) for the change in Ros required to exclude natural variability were 0.39, 0.50 and 0.53 cmH2O l-1 s, respectively. There was a small fall in Ros in response to salbutamol although the mean maximum change (0.46 cmH2O l-1 s) was not significant (by ANOVA). Thus, the change in Ros (sensitivity) was no greater than the 95% confidence value for natural variability (reproducibility). Regression analysis also showed no evidence of a dose-response relationship for Ros.     

Risks versus benefits of inhaled beta 2-agonists in the management of asthma.

The therapeutic goal for the treatment of asthma should be to suppress bronchial mucosal inflammation with preventive drugs such as inhaled corticosteroids, and to relieve symptoms of wheezing and breathlessness with bronchodilator drugs. The lower recommended doses of inhaled beta 2-agonists produce rapid effective bronchodilatation without systemic adverse effects; higher doses may produce substantial improvements in airway response which may help patients with more severe airflow obstruction. Higher doses of inhaled beta 2-agonists also cause dose-related systemic adverse beta 2 effects including tremor, tachycardia, hypokalaemia and associated electrocardiographic sequelae. In this respect, although fenoterol appears to cause greater extrapulmonary beta 2-mediated adverse effects at higher doses, there is no evidence to suggest that it is any less beta 2-selective. There is also some evidence to suggest that use of regular inhaled beta 2-agonists may cause increased bronchial hyperreactivity and possibly deterioration in disease control. Patients who require such regular use should therefore be given additional anti-inflammatory therapy with inhaled corticosteroids. The recent availability of novel, longer-acting inhaled beta 2-agonists such as salmeterol and formoterol will also make necessary a careful reappraisal of their long term use in patients with asthma.     

Effects of fexofenadine and desloratadine on subjective and objective measures of nasal congestion in seasonal allergic rhinitis

BACKGROUND: In vitro studies have shown much higher H1-receptor antagonist potency with desloratadine (DL) compared to fexofenadine (FEX), although it is unclear whether this has any clinical relevance on disease control parameters in seasonal allergic rhinitis (SAR), especially for nasal congestion. OBJECTIVE: To compare the relative efficacy between presently recommended doses of DL and FEX on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in SAR. METHODS: Forty-nine patients with SAR were randomized into a double-blind, placebo-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the morning. There was a 7-10 day placebo run-in and washout prior to each randomized treatment. Measurements were made in the morning (AM) and in the evening (PM) for PNIF (the primary outcome variable), nasal and eye symptoms. The average of AM/PM values were used for analysis. RESULTS: There were significant (P < 0.05) improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage, nasal irritation, and total nasal symptoms, but not nasal discharge or eye symptoms. There were no significant differences between active treatments. Values for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI for difference) were 126, 10 (4-16) for FEX; and 122, 11 (4-17) for DL. The mean difference (95% CI) between FEX vs. DL was 1 L/min (-7-8). Values for total nasal symptoms (out of 12) were: 3.2, 0.7 (0.2-1.2) for FEX; and 3.4, 0.9 (0.3-1.5) for DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1-0.4) for FEX; and 1.2, 0.3 (0.1-0.5) for DL. The mean difference (95% CI) in total nasal symptoms and nasal blockage between FEX vs. DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3), respectively. CONCLUSIONS: Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR.