Pulmonary Artery Pressure in Rats with Hereditary Platelet Function Defect

Abstract

Pulmonary vasoactivity of several biochemical components produced or stored in platelet was the justification for the study of pulmonary artery pressure in fawn-hooded rats (FHR) with hereditary platelet storage pool deficiency. Anesthetized (pentobarbital 35 mg kg^-1 i.p.) FHR had higher right ventricular systolic pressure compared with normal Wistar rats (NWR) matched in sex and age (57.7 ± 6,8 vs. 34.8 ± 1.2 mm Hg; p < 0.01). The incidence of higher pulmonary artery pressure ( > x + 2 SD of NWR) was 68% among FHR. A significant difference was recorded between FHR and NWR in the relative weight of the right ventricle (0.092 ± 0.021 vs. 0.048 ± 0.001 g/100 g; p < 0.05). Rise in pulmonary artery pressure in FHR after 4 weeks of normobaric hypoxia was found to be comparable to that seen posthypoxically in NWR. Morphological consequences of pulmonary hypertension, ranging from moderate medial hypertrophy of small arteries to muscularization of pulmonary arterioles, were recorded in about 50% of FHR with increased pulmonary artery pressure

cAMP activates BKCachannels in pulmonary arterial smooth muscle via cGMP-dependent protein kinase

“…Recently, the FHR has been found to be an excellent animal model to study pulmonary hypertension (22,36). The FHR strain is characterized by platelet abnormalties and systemic hypertension and has been widely used to study genetic risk factors for the development of idiopathic pulmonary hypertension (20,36). Studies show that the platelet storage disease is not involved in the pathogenesis of pulmonary hypertension (2,20) and that the FHR strain develops significant pulmonary hypertension, which is not associated with differences in blood gas tension, polycythemia, or parenchymal lung disease (45).…”

“…The FHR strain is characterized by platelet abnormalties and systemic hypertension and has been widely used to study genetic risk factors for the development of idiopathic pulmonary hypertension (20,36). Studies show that the platelet storage disease is not involved in the pathogenesis of pulmonary hypertension (2,20) and that the FHR strain develops significant pulmonary hypertension, which is not associated with differences in blood gas tension, polycythemia, or parenchymal lung disease (45). Unlike other rat strains, FHR develop severe pulmonary hypertension, which is age dependent (20), a phenomenon accelerated under mild hypoxic conditions (36).…”

“…Studies show that the platelet storage disease is not involved in the pathogenesis of pulmonary hypertension (2,20) and that the FHR strain develops significant pulmonary hypertension, which is not associated with differences in blood gas tension, polycythemia, or parenchymal lung disease (45). Unlike other rat strains, FHR develop severe pulmonary hypertension, which is age dependent (20), a phenomenon accelerated under mild hypoxic conditions (36). Evidence also suggests that the genetic locus for the hypertensive condition is PH1 on chromosome 1 (39).…”

Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1α-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer

“…Moreover, most models evolve rapidly (in 2 wk) in response to a single extrinsic toxic stimulus (monocrotaline, hypoxia, etc). The fawn-hooded rat (FHR), a mutant strain named for its brown mantle of fur, is unique in spontaneously developing PAH (42). FHR PAH is heritable (84) with high penetrance (42).…”

“…The fawn-hooded rat (FHR), a mutant strain named for its brown mantle of fur, is unique in spontaneously developing PAH (42). FHR PAH is heritable (84) with high penetrance (42). FHR typically die of slowly evolving PAH at ϳ1 yr of age; notably PAH is absent until age 20 wk (20).…”