angiotensin-i and Edema

Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (

Topics: Angiotensin I; Animals; Biological Availability; Biomarkers; Blood Pressure; Cardiomyopathy, Dilated; Cyclic GMP; Diet, Sodium-Restricted; Edema; Heart Failure; Kidney; Male; Mice, Inbred C57BL; Natriuretic Peptide, Brain; Nitric Oxide; Nitric Oxide Synthase; Peptide Fragments; Phosphoric Diester Hydrolases; Pleural Effusion; Renin-Angiotensin System; Survival Analysis; Systole

Studies have shown that angiotensin-converting enzyme 2 (ACE2) plays modulating roles in lung pathophysiology, including pulmonary fibrosis (PF) and acute lung injury. Pulmonary fibrosis is a common complication in these interstitial lung diseases, and PF always has a poor prognosis and short survival. To date, there are few promising methods for treating PF, and they are invariably accompanied by severe side effects. Recent studies have showed that the traditional Chinese herbal extract, osthole, had beneficial effects on lipopolysaccharide (LPS) induced acute lung injury (ALI) via an ACE2 pathway. Here we further investigated the protective effects of osthole on bleomycin induced pulmonary fibrosis and attempted to determine the underlying mechanism. PF mode rats were induced by bleomycin (BLM) and then subsequently administered osthole. Histopathological analyses were employed to identify PF changes. The results showed that BLM resulted in severe PF and diffuse lung inflammation, together with significant elevation of inflammatory factors and a marked increase in expression of angiotensin II (ANG II) and transforming growth factor-beta 1 (TGF-β1). ACE2 and angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. Meanwhile, osthole treatment attenuated BLM induced PF and inflammation, decreased the expression of these inflammatory mediators, ANG II, and TGF-β1, and reversed ACE2 and ANG-(1-7) production in rat lungs. We conclude that osthole may exert beneficial effects on BLM induced PF in rats, perhaps via modulating the ACE2/ANG-(1-7) axis and inhibiting lung inflammation pathways.

Topics: Acute Lung Injury; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Anti-Inflammatory Agents; Bleomycin; Collagen; Coumarins; Cytokines; Edema; Lung; Male; Peptide Fragments; Peptidyl-Dipeptidase A; Pulmonary Fibrosis; Rats, Sprague-Dawley; Transforming Growth Factor beta1

32 out of 83 in patients with atopic dermatitis showed a decrease of urine excretion during acute exacerbation and elevated levels of antidiuretic hormone (ADH 23 of 29 cases), renin (18 of 32 cases), angiotensin (22 of 29 cases) and aldosterone (16 of 37 cases). Six cases with high ADH showed severe pitting edema of lower legs with hypoalbuminemia. ADH, volume of urine and edema were improved when their skin symptoms subsided. There was no statistically significant relationship between the dose of steroid ointment and ADH. Also there was no correlation between low 17-OHCS or 17-KS and high ADH or renin.

Topics: Adult; Aldosterone; Angiotensin I; Dermatitis, Atopic; Edema; Female; Humans; Male; Renin; Vasopressins

The pharmacological properties of FK 739, a new angiotensin II-receptor antagonist, were examined. FK 739 inhibited the specific binding of [125I]-angiotensin II to rat aortic smooth muscle cell membrane with an IC50 value of 8.6 nM, but did not displace the specific binding of [125I]-angiotensin II to bovine cerebellum membrane. In isolated helical strips of rabbit aorta, FK 739 shifted the concentration-response curve of angiotensin II-induced contraction in parallel to the right, and the values of the slope and pA2 were 1.06 and 8.45, respectively. In in vivo studies, oral administration of FK 739 at 10 mg/kg significantly inhibited the angiotensin I-induced pressor response in normotensive rats and dogs, and it caused a fall of mean blood pressure in renal hypertensive rats and dogs. In spontaneously hypertensive rats, FK 739 at 32 and 100 mg/kg significantly decreased the mean blood pressure in a dose-dependent manner. Additionally, we studied whether FK 739 would cause side effects such as dry cough, like other ACE inhibitors did. Oral administration of FK 739 (10 and 32 mg/kg) did not affect the capsaicin-induced bronchial edema. On the other hand, captopril (10 mg/kg) significantly enhanced capsaicin-induced bronchial edema. These results indicate that FK 739 is a potent and competitive antagonist for AT1-type receptors, and suggest that FK 739 might be a safe and useful agent for the treatment of hypertension in clinical trials.

Topics: Angiotensin I; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Blood Pressure; Bronchial Diseases; Cattle; Cell Membrane; Cerebellum; Dogs; Edema; Guinea Pigs; Hypertension; Hypertension, Renovascular; Imidazoles; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth, Vascular; Pyridines; Rabbits; Rats; Rats, Inbred SHR; Rats, Wistar

Carrageenin-induced oedema in rats was potentiated by oral administration of (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (SA291) and related sulfhydryl compounds, and the effect was closely correlated with their potencies as inhibitors of angiotensin-converting enzyme in vivo.

Topics: Angiotensin I; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Carrageenan; Dose-Response Relationship, Drug; Drug Synergism; Edema; Male; Rats; Sulfhydryl Compounds; Thiazoles