Vasorelaxant effect of glucagon-like peptide-(7-36)amide and amylin on the pulmonary circulation of the rat.

The gastrointestinal peptides glucagon-like peptide-1(7-36)amide (GLP-1) and amylin are currently being tested in clinical trials for the treatment of diabetes mellitus due to their effects in lowering blood glucose. Receptors for these polypeptides also exist in the lung and since polypeptides are known to modulate airway and pulmonary vascular tone, we investigated whether GLP-1 and amylin act similarly in the lung. We compared their effects with the well-known actions of calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP). Both GLP-1 and amylin induced a dose-dependent and time-reversible endothelial-dependent relaxation of preconstricted pulmonary artery rings. Amylin was approximately as strong as VIP and CGRP, GLP-1 however, was 2.3-fold less potent. GLP-1 as well as amylin also reduced the vascular tone in the isolated, perfused and ventilated rat lung. In contrast to their action on the pulmonary vasculature, neither GLP-1 nor amylin showed any effect on the tone of isolated preconstricted trachea rings. In conclusion, GLP-1 and amylin represent two additional peptides which may modulate pulmonary vascular tone.

[Nocturnal hypertension and sleep apnea: effect of the ACE inhibitor cilazapril on apnea-induced blood pressure increases during sleep]. / Nächtliche Hypertonie und Schlafapnoe: Effekt des ACE-Hemmers Cilazapril auf apnoe-induzierte Blutdruckanstiege im Schlaf.

The nocturnal increases in blood pressure in cases of obstructive sleep apnea are discussed as causes in connection with increased cardiovascular mortality in sleep apnea. Previous antihypertension therapy studies revealed the antihypertensive action of the ACE inhibitor cilazapril averaged over NREM (NR) and REM sleep (R). In the present study, the effect of this drug on the blood pressure increase within the stress segment of obstructive apnea in NR and R was investigated in a double-blind randomized study versus placebo. Data were collected in digital form with the help of cardiorespiratory polysomnography and intra-arterial blood pressure measurements; a total of 640 apnea in 16 patients were evaluated. Relevant increases in blood pressure occurred during the apnea which were, as expected, more pronounced in R (150/74 mmHg) than in NR (135/69 mmHg). The antihypertensive action of cilazapril was also stronger in R (systole--11.9/diastole--6.4 mmHg) than in NR (systolic--9.0 mmHg/diastolic--5.7 mmHg). Placebo caused significantly lower decreases in blood pressure (systolic--3.7 mmHg/diastolic--2.4 mmHg in R, systolic--2.8 mmHg/diastolic--1.8 mmHg in NR). Thus, evidence is provided for a clinically relevant blood pressure lowering effect of the drug cilazapril on the stress-induced blood pressure increases accompanying obstructive apnea both in NREM and in REM sleep.

Lipoprotein (a), low-density, intermediate-density lipoprotein, and blood pressure in a young male population.

Both hypercholesterolemia and hypertension are risk factors for atherosclerotic vascular disease, and elevated cholesterol levels occur more frequently than expected in patients with hypertension. Elevated levels of intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL) were shown to be atherogenic, and LDL, comprising the major cholesterol-carrying fraction in human plasma, are structurally related to lipoprotein (a)[Lp(a)], a further risk factor for atherosclerosis. In the present study we investigated 200 male employees (mean age 26 +/- 7 years) to determine whether the relationship of IDL and Lp(a) to systemic blood pressure is similar to the reported correlations between total and LDL cholesterol and systemic blood pressure. To this end blood pressure was measured several times in each individual, and lipids, lipoprotein-cholesterol, apolipoprotein B (apo B), and Lp(a) were determined in fasting serum. IDL cholesterol and apo B, the main protein component of IDL and LDL correlated with blood pressure. However, levels of Lp(a) correlated neither with systolic or diastolic blood pressure nor with lipoprotein cholesterol, body weight, or age. Although IDL and Lp(a) are considered lipoprotein risk factors for atherosclerosis, levels of Lp(a), unlike IDL, are not related to blood pressure, body weight, or age. Our data suggest different metabolic and pathophysiological mechanisms of the risk factors, IDL, LDL, and Lp(a).

Lung injury in acute experimental pancreatitis in rats. II. Functional studies.

In this study we report the functional changes in isolated perfused lungs from rats with cerulein-induced experimental pancreatitis. Rat lungs isolated immediately after the cerulein infusion demonstrated decreased pressor responses to angiotensin II (A II) and acute hypoxia (FIO2: 0.0). The lung wet- to dry-weight ratio was increased, as was the lung-leak index, consistent with high-permeability edema formation in the lung. Neither saline-solution infusion for 12 h nor perfusion with cerulein of rat lungs isolated from untreated animals caused lung injury or functional alterations. The changes in pulmonary vascular reactivity were normalized 48-72 h after induction of pancreatitis. In conclusion, we describe an animal model of pancreatitis and reversible, ARDS-like lung injury.

Precipitins to inhaled avian antigens: results of an inter-laboratory study.

Precipitins against avian antigens in sera from patients with extrinsic allergic alveolitis, asymptomatic pigeon and chicken breeders and from control individuals were tested with different antigen extracts in six laboratories by a variety of different methods. Eighty percent of the results coincided in identifying the positive sera from patients and 90% in identifying the controls. It seems possible therefore to exchange results among experienced laboratories with fair confidence.

In vivo inhibition of phospholipase A2 in rat lung by an beta-adrenergic agonist.

Phospholipase A2 is the key enzyme for the release of arachidonic acid derived mediators via cycloxygenase or lipoxygenase pathways in inflammation and immunological processes. Activity of microsomal phospholipase A2 in rat lung can be inhibited by in vivo application of the beta-adrenergic drug fenoterol both in control and diseased animals.

Alveolar stability and phospolipid content in normal pig lungs and in pig lungs with Mycoplasma pneumonia.

In pig lungs with enzootic pneumonia (a mycoplasma infection) a considerably higher phospholipid content was measured than in normal lungs, in spite of a reduced surfactant function in these lungs.