| Postnatal intermittent hypoxia and developmental programming of hypertension in spontaneously hypertensive rats: the role of reactive oxygen species and L-Ca2+ channels. | |
| | |
MedLine Citation:
|
PMID: 18474836 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Obstructive and central apneas during sleep are associated with chronic intermittent hypoxia (CIH) and increased cardiovascular morbidity. Spontaneously hypertensive rats exposed to CIH during postnatal days 4 to 30 develop exaggerated hypertension as adults. We hypothesized that reactive oxygen species and altered L-Ca(2+) channel activity may underlie the postnatal programming of exaggerated blood pressure and cardiac remodeling. Newborn male spontaneously hypertensive rats were exposed to CIH (10% and 21% O(2) alternating every 90 seconds, 12 h/d, for postnatal days 4 to 30) or normoxia (room air). In each condition, spontaneously hypertensive rats received daily (SC) 1 of 3 treatments: L-calcium channel blocker nifedipine (5 mg/kg), superoxide dismutase mimetic MnTMPyP pentachloride (10 mg/kg), or vehicle (polyethylene glycol). Blood pressure was evaluated monthly for 6 months after birth, and echocardiographic assessments were conducted at 6 months of age. CIH vehicle-treated rats presented higher systolic blood pressure (187+/-5 mm Hg) as compared with normoxic vehicle treated controls (163+/-2 mm Hg; P<0.001). Postnatal CIH elicited marked increases in left ventricular wall thickness in a pattern of concentric hypertrophy with augmented systolic contractility. The treatment with nifedipine in the CIH group attenuated blood pressure (159+/-2 mm Hg; P<0.001) and normalized left ventricular wall thickness and systolic function, whereas the treatment with SOD mimetic decreased blood pressure (165+/-2 mm Hg; P<0.001) and reduced left ventricular wall thickness without changes in the systolic function. We conclude that Ca(2+) and reactive oxygen species-mediated signaling during intermittent hypoxia are critical mechanisms underlying postnatal programming of an increased severity of hypertension and hypertrophic cardiac remodeling in a genetically susceptible rodent model. |
| | |
Authors:
|
Galia K Soukhova-O'Hare; Roger V Ortines; Yan Gu; Alexander D Nozdrachev; Sumanth D Prabhu; David Gozal |
Related Documents
:
|
2328526 - Nitrate tolerance: hemodynamic effects of intravenous isosorbide dinitrate after sustai... 8206566 - Blood pressure inversely correlates with thrombin-evoked calcium rise in platelets. 2258886 - Acute and long-term treatment of hypertension with nifedipine in the elderly. 8270176 - The topical application of verapamil and nifedipine lowers intraocular pressure in cons... 822136 - Primate model of cerebral hematoma. 21522096 - Role of magnesium sulphate in the treatment of hypomagnesaemia in eclamptic patients. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-05-12 |
Journal Detail:
|
Title: Hypertension Volume: 52 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2008 Jul |
Date Detail:
|
Created Date: 2008-06-20 Completed Date: 2008-07-08 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
|
Languages: eng Pagination: 156-62 Citation Subset: IM |
Affiliation:
|
Kosair Children's Hospital Research Institute, University of Louisville, KY 40202, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Anoxia / complications* Antioxidants / pharmacology Blood Pressure / drug effects Body Weight Calcium Channel Blockers / pharmacology Calcium Channels, L-Type / drug effects, metabolism* Echocardiography Heart Rate / drug effects Heart Ventricles / drug effects, physiopathology, ultrasonography Hypertension / etiology*, metabolism*, prevention & control Lipid Peroxides / analysis Male Metalloporphyrins / pharmacology Nifedipine / pharmacology Rats Rats, Inbred SHR Reactive Oxygen Species / metabolism* Ventricular Remodeling / drug effects |
| Grant Support | |
ID/Acronym/Agency:
|
2P50HL60296/HL/NHLBI NIH HHS; ES11860/ES/NIEHS NIH HHS; F32HL70494/HL/NHLBI NIH HHS; HL078825/HL/NHLBI NIH HHS; HL65270/HL/NHLBI NIH HHS; HL69932/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antioxidants; 0/Calcium Channel Blockers; 0/Calcium Channels, L-Type; 0/Lipid Peroxides; 0/Metalloporphyrins; 0/Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; 0/Reactive Oxygen Species; 21829-25-4/Nifedipine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Left ventricular filling pressure by Doppler echocardiography in patients with end-stage renal disea...
Next Document: Education Research: The challenge of incorporating formal research methodology training in a neurolo...