RGD Reference Report - Attenuation of chronic hypoxic pulmonary hypertension by simvastatin. - Rat Genome Database

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Attenuation of chronic hypoxic pulmonary hypertension by simvastatin.

Authors: Girgis, RE  Li, D  Zhan, X  Garcia, JG  Tuder, RM  Hassoun, PM  Johns, RA 
Citation: Girgis RE, etal., Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H938-45. Epub 2003 May 15.
RGD ID: 5508701
Pubmed: PMID:12750068   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.01097.2002   (Journal Full-text)

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to improve multiple normal endothelial cell functions and inhibit vascular wall cell proliferation. We hypothesized that one such agent, simvastatin, would attenuate chronic hypoxic pulmonary hypertension. Male adult Sprague-Dawley rats were exposed (14 days) to normoxia (N), normoxia plus once-a-day administered simvastatin (20 mg/kg ip) (NS), hypoxia (10% inspired O2 fraction) (H), or hypoxia plus simvastatin (HS). Mean pulmonary artery pressure, measured in anesthetized, ventilated rats with an open-chest method, was reduced from 25 +/- 2 mmHg in H to 18 +/- 1 in HS (P < 0.001) but did not reach normoxic values (12 +/- 1 mmHg). Similarly, right ventricular/left ventricular plus interventricular septal weight was reduced from 0.53 +/- 0.02 in the H group to 0.36 +/- 0.02 in the HS group (P < 0.001). The increased hematocrit in H (0.65 +/- 0.02) was prevented by simvastatin treatment (0.51 +/- 0.01, P < 0.001). Hematocrit was similar in N versus NS. Alveolar vessel muscularization and medial thickening of vessels 50-200 microM in diameter induced by hypoxia were also significantly attenuated in the HS animals. Lung endothelial nitric oxide synthase (eNOS) protein expression in the HS group was less than H (P < 0.01) but was similar in N versus NS. We conclude that simvastatin treatment potently attenuates chronic hypoxic pulmonary hypertension and polycythemia in rats and inhibits vascular remodeling. Enhancement of lung eNOS expression does not appear to be involved in mediating this effect.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pulmonary hypertension  ISOHmgcr (Rattus norvegicus)5508701; 5508701 RGD 
pulmonary hypertension  IMP 5508701 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hmgcr  (3-hydroxy-3-methylglutaryl-CoA reductase)

Genes (Mus musculus)
Hmgcr  (3-hydroxy-3-methylglutaryl-Coenzyme A reductase)

Genes (Homo sapiens)
HMGCR  (3-hydroxy-3-methylglutaryl-CoA reductase)


Additional Information