Effects of PDE-5 inhibition on the cardiopulmonary system after 2 or 4 weeks of chronic hypoxia
Articolo
Data di Pubblicazione:
2019
Citazione:
Effects of PDE-5 inhibition on the cardiopulmonary system after 2 or 4 weeks of chronic hypoxia / C. Nydegger, A. Corno, L. von Segesser, M. Beghetti, M. Samaja, G. Milano. - In: CARDIOVASCULAR DRUGS AND THERAPY. - ISSN 1573-7241. - (2019). [Epub ahead of print]
Abstract:
Purpose In pulmonary hypertension (PH), hypoxia represents both an outcome and a cause of exacerbation.We addressed the question
whether hypoxia adaptation might affect the mechanisms underlying PH alleviation through phosphodiesterase-5 (PDE5) inhibition.
Methods Eight-week-old male Sprague-Dawley rats were divided into two groups depending on treatment (placebo or sildenafil,
a drug inhibiting PDE5) and were exposed to hypoxia (10% O2) for 0 (t0, n = 9/10), 2 (t2, n = 5/5) or 4 (t4, n = 5/5) weeks. The
rats were treated (0.3 mL i.p.) with either saline or sildenafil (1.4 mg/Kg per day).
Results Two-week hypoxia changed the body weight (− 31% vs. − 27%, respectively, P = NS), blood hemoglobin (+ 25% vs. +
27%, P = NS) and nitrates+nitrites (+ 175% vs. + 261%, P = 0.007), right ventricle fibrosis (+ 814% vs. + 317%, P < 0.0001),
right ventricle hypertrophy (+ 84% vs. + 49%, P = 0.007) and systolic pressure (+ 108% vs. + 41%, P = 0.001), pulmonary vessel
density (+ 61% vs. + 46%, P = NS), and the frequency of small (< 50 µm wall thickness) vessels (+ 35% vs. + 13%, P = 0.0001).
Most of these changes were maintained for 4-week hypoxia, except blood hemoglobin and right ventricle hypertrophy that
continued increasing (+ 52% vs. + 42%, P = NS; and + 104% vs. + 83%, P = 0.04). To further assess these observations, small
vessel frequency was found to be linearly related with the right ventricle-developed pressure independent of hypoxia duration.
Conclusions Thus, although hypoxia adaptation is not yet accomplished after 4 weeks, PH alleviation by PDE5 inhibition might
nevertheless provide an efficient strategy for the management of this disease
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Chronic hypoxia . Adaptation . Phosphodiesterase-5 inhibition . Pulmonary angiogenesis . Right-ventricle hypertrophy
Elenco autori:
C. Nydegger, A. Corno, L. von Segesser, M. Beghetti, M. Samaja, G. Milano
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