We investigated whether endothelial dysfunction might contribute to the exaggerated vasoconstriction that was induced by the administration of norepinephrine at the early stage of one-kidney, one-clip renal hypertension (1K1C) in rats. We also studied the role of the renin-angiotensin system in this phenomenon. Male Wistar rats were killed 48 hours after the induction of renal artery stenosis or sham operation, and ring preparations of the thoracic aorta were obtained. The isometric contraction and relaxation of aortic strips produced by norepinephrine and acetylcholine, respectively, were recorded with a force-displacement transducer. The aorta of 1K1C rats showed a significantly (P<.05) exaggerated contractile response to norepinephrine as compared with that of control rats. Rubbing the endothelium and treatment with methylene blue or N0-monomethyl L-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in Although an increased vascular reactivity to vaso-L.1 constrictor substances has been observed both in clinical hypertension",2 and in animal models of hypertension,3-9 the mechanisms are not completely understood. Folkow et al10 suggest that this hyperresponsiveness in hypertension is due to vascular wall hypertrophy or medial hypertrophy that results in an increased vessel wall to lumen ratio. Findings of other investigators4,5"11 indicate that such mechanisms are not the only explanation. For instance, Prewitt et al"l reported that no vascular wall hypertrophy was observed in resistance vessels of one-kidney, one-clip renal hypertensive (iKiC) rats, despite a structural reduction in the size of the lumen. Others45 have reported that an exaggerated pressor response and increased sensitivity (change in threshold) to norepinephrine occur in rabbits with renal artery stenosis at an early stage, even before the onset of hypertension. These studies4,5"11 indicate that the exaggerated pressor response may be due to some alteration in the responsiveness of the vessels without hypertrophy of the vascular wall and suggest that the responsiveness of the vascular smooth muscle cells itself may be enhanced. However, confirmatory evidence is lacking.Received February 18, 1993; accepted October 8, 1993 Our objective was to determine the role of depressed synthesis and/or release of EDRF on the exaggerated vasoconstrictive response to norepinephrine at the early stage of hypertension before the development of vascular wall hypertrophy or an increased vascular wall to lumen ratio. The present study was designed to clarify the role of the renin-angiotensin system in endothelial by guest on
The level of nitric oxide (NO) in exhaled air fluctuates in normal individuals depending on the physiological conditions. We evaluated the effects of duration of exhalation and breath-holding on the exhaled concentrations of NO in 16 normal human volunteers. Exhaled gas corresponding to vital capacity was collected in 6-liter Tedlar bags and analyzed by chemiluminescence. The NO concentration in exhaled gas increased significantly in proportion to the duration of exhalation [P = 0.009 +/- 0.011 (SD)] and was increased after breath-holding. There was no significant difference in the exhaled NO concentration among 10-s phases of a 30-s exhalation, as determined from multiple breath collections. The NO released from the airways is presumably unaffected by fluctuation of exhalation speed. The NO release rate, calculated from a single regression analysis between the NO concentration and the duration of exhalation, was 39 +/- 29 pmol/s, a value which was about fourfold greater in nine patients with bronchial asthma.
We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate, to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), N G -nitro-L-arginine methyl ester (L-NAME) 500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50 mg/L or 100 mg/L in the drinking water (n ؍ ؍ 10 -12). We then collected 24-h urine samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90 ؎ ؎ 0.65 v 0.05 ؎ ؎ 0.02 mg/day/100 g in control), and the area of the left ventricular wall (83.3 ؎ ؎ 3.0 v 69.8 ؎ ؎ 1.8 mm 2 in control). Nephrosclerosis and myocardial interstitial fibrosis were documented histologically. The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure, the LVH (70.8 ؎ ؎ 1.8 mm 2 ), the albuminuria (0.05 ؎ ؎ 0.01 mg/day/100 g), and the histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME-induced effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in rats produced nephrosclerosis and LVH that were effectively prevented by giving imidapril at a dose lower than that of amlodipine. We conclude that ACE inhibitors can prevent nephrosclerosis and LVH even in the presence of a reduction in NO production, implying that in rats the inhibition of the renin-angiotensin system is more effective than the blockade of calcium channels in preventing hypertensive tissue injury. Am J Hypertens 1998;11:697-707
A 57-year-old female patient with Sjogren's syndrome was complicated with pulmonary hypertension (PH) and antiphospholipid antibody (aPL). She had a history offetal losses, deep vein thrombosis and chronic thyroiditis. On admission, severe pulmonary hypertension, thrombocytopenia, lupus anticoagulant and a decreased level of protein C were found. Pulmonary artery per fusion scintigram revealed multiple defects. She died suddenly despite an intensive therapy. Intimal proliferation with angiomatoid lesions in small pulmonary arteries was observed by autopsy. Since a close relationship between PH and aPL in connective tissue disease is found, it is important to carefully analyze the antiphospholipid antibodies in patients with PH. (Internal Medicine 33: 768-772, 1994)
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