No abstract

Ferreira & Vane (1967) have shown that less than 30% of bradykinin infused into the right atrium emerges in the ascending aorta. In blood the biological half-life was found to be 17 sec. Considering the brief circulation time from right atrium to ascending aorta (2-lOsec.; Spector, 1956), they concluded that enzymes of blood could not account for the degree of inactivation that occurred in the pulmonary circulation.A possible mechanism for the pulmonary inactivation of bradykinin is through hydrolysis by enzymes at or near the vascular endothelium. We have begun an investigation of this possibility by using a rat lung preparation in situ washed free of blood.Rats, weighing 0-2-0-4kg., were anaesthetized with pentobarbital (50mg./kg. body wt.) given by intraperitoneal injection. Polythene cannulae were placed in the left common carotid artery and the right external jugular vein. Another cannula was placed in the trachea and the lungs were ventilated mechanically. Saline (0.9% NaCI) was infused into the venous cannula and the rat was exsanguinated through the arterial cannula. Then a cannula was inserted through a slit in the right ventricle into the pulmonary artery and another was tied into the left ventricle.A Locke dextran solution (11. contained: dextran, 40g.; NaCl, 9 0g.; KCl, 0-42g.; CaCl2, 0-24g.; D-glucose, 10g.; NaHCO3, 0.2g.) was infused into the pulmonary artery at a rate of 4ml./min. and the effluent was collected from the cannula in the left ventricle. The infusion solutions were heated at 370 and were aerated with 02 + CO2 (95: 5). When the effluent became free of erythrocytes (after 30-40min.) [2-L-proline-14C]bradykinin (28.6 ,uc/mg., lot no. 307-64; New England Nuclear Corp., Boston, Mass., U.S.A.) in Locke dextran solution was infused. The infusion rate was maintained at 4ml./min. Bradykinin was infused at 2-0 or 4 0,ug./ min. In one experiment it was infused at 100lg./ min. In another experiment 2-mercaptoethanol (1.5mg./ml.) was added to the Locke dextran solution. In each of these experiments bradykinin was infused for 20min.The effluent from the left ventricle was collected in an Erlenmeyer flask containing lOOml. of 4%(v/v) trifluoroacetic acid. The vessel contents were stirred constantly with a magnetic stirring apparatus. After the infusion had been stopped the effluent was concentrated to 10-20ml. in a rotary evaporator. This viscous solution was extracted four times with equal volumes of butan-1-ol previously equilibrated with 2% trifluoroacetic acid. Under these conditions the apparent partition coefficient of bradykinin is greater than 1 0 whereas the apparent partition coefficient of dextran is less than 0-1. The butan-l-ol extract was evaporated to dryness and the residue was resuspended in lOml. of 2% trifluoroacetic acid previously equilibrated with butan-1-ol. The butan-1-ol extraction was repeated and the butan-l-ol extract was evaporated to dryness. The residue was redissolved in 1 0ml. of 6% (v/v) acetic acid. A sample (0. 1-0. 5 ml.) of this solution was applied to the centr...

OBJECTIVE:To determine the point prevalence of pulmonary hypertension (PH) and its relationship with respiratory disturbances in obese patients living at moderate altitude. SUBJECTS: A total of 57 obese patients comprised the final sample and consisted of 34 women and 23 men, with a mean age of 42.7712.1 ys and a mean body mass index (BMI) 47.1710.6 kg/m 2 (range from 30.1 to 76.1). The mean living altitude was 2248.7 m, range 2100-2400 m above sea level. MEASUREMENTS: Doppler echocardiography, pulmonary function tests, arterial blood gas analysis, and polysomnography were performed. RESULTS: Data showed that 96.5% of the studied sample had daytime PH defined as calculated systolic pulmonary artery pressure (PSAP) 430 mmHg (mean PSAP ¼ 50, s.d. ¼ 13 mmHg). The severity of diurnal PH was found to be related to the presence of alveolar hypoventilation and BMI. The main risk factor for severity of diurnal PH was hypoventilation with a significant odds ratio (OR) 7.96, 95% CI 1.35-46.84, BMI was (OR 1.12, 95% CI 1.02-1.25) and apnea/hypopnea index was not a predictor of pulmonary hypertension severity (OR 0.99, 95% CI 0.97-1.02). CONCLUSION: We concluded that prevalence of diurnal PH is high in obese patients living at moderate altitude, and that hypoventilation is the main risk factor associated with the severity of pulmonary hypertension.

In the perfusate and the urine produced during perfusion of isolated rat kidneys a kallikreinlike enzyme similar to that found in the kidney was detectable by bioassay 15-25 min after the beginning of the perfusion. The source of the kallikrein activity was the kidney itself, since before the perfusion was started the blood remaining in the kidneys was washed out and the perfusion medium was free of kallikrein and its precursors and substrates. The kallikreinlike activity of the perfusate was characterized by a) an oxytocic effect on isolated rat uterus, b) a kininogenase activity on kininogen II, c) an esterase activity on N-benozyl-L-arginine ethyl ester, and d) a hypotensive effect on anethetized rats. These properties were inhibited by diisopropyl activity in the perfused kidney was lower than that in the nonperfused organ, but the total amount of kallikrein activity released to the excreted urine and the perfusate was significantly greater than the corresponding activity that disappeared in the kidney. This result is in keeping with the concept that the renal tissue is able to synthesize kallikrein.

1. Urinary kallikrein excreted by normal rats is significantly increased (P <0.001) 2 h after: (a) water loading, (b) water loading plus frusemide, 0.27 mmol (10 mg) per rat, (c) salt loading. In water-loaded rats, 5 i.u. of renin strikingly reduced kallikrein excretion (P < 0.01) but considerably increased sodium excretion (P150 mmHg) showed no increase of urinary kallikrein after water loading, although there was a marked natriuresis; in moderately hypertensive rats (blood pressure < 150 mmHg) urinary kallikrein was only one-third of that observed in control normotensive rats, after an equal degree of water loading.