Document Detail


Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: role of fasudil, a Rho kinase inhibitor.
MedLine Citation:
PMID:  23344570     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure (MAP) and renal function were determined in conscious animals pretreated with enalapril (250 mg/l in drinking water) for 1 wk to block the endogenous renin-angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100 ng·kg(-1)·min(-1)) induced a greater increase in MAP and renal vascular resistance and enhanced reduction in glomerular filtration rate in intact male growth-restricted rats compared with intact male controls (P < 0.05). Cotreatment with the Rho kinase inhibitor fasudil (33 μg·kg(-1)·min(-1)) significantly attenuated these hemodynamic changes (P < 0.05), but it did not abolish the differential increase in blood pressure above baseline, suggesting that the impact of intrauterine growth restriction on blood pressure in intact male growth-restricted rats is independent of Rho kinase. Gonadectomy in conjunction with fasudil returned blood pressure back to baseline in male growth-restricted rats, and yet glomerular filtration rate remained significantly reduced (P < 0.05). Thus, these data suggest a role for enhanced renal sensitivity to acute Ang II in the developmental programming of hypertension in male growth-restricted rats. However, inhibition of Rho kinase had no effect on the basal or enhanced increase in blood pressure induced by acute Ang II in the gonadectomized female growth-restricted rat. Therefore, these studies suggest that Rho kinase inhibition exerts a sex-specific effect on blood pressure sensitivity to acute Ang II in growth-restricted rats.
Authors:
Norma B Ojeda; Thomas P Royals; Barbara T Alexander
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-23
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  304     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-02     Completed Date:  2013-05-23     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F900-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*,  pharmacology
Angiotensin II / pharmacology*
Animals
Blood Pressure / drug effects*
Castration
Enalapril / pharmacology
Female
Fetal Growth Retardation / physiopathology*
Glomerular Filtration Rate / drug effects
Hemodynamics / drug effects
Kidney / drug effects,  physiopathology
Male
Placental Insufficiency / physiopathology
Pregnancy
Prenatal Exposure Delayed Effects / physiopathology
Rats
Renal Circulation / drug effects
Renin-Angiotensin System / drug effects
Sex Characteristics
Vascular Resistance / drug effects
rho-Associated Kinases / antagonists & inhibitors,  physiology*
Grant Support
ID/Acronym/Agency:
HL-074927/HL/NHLBI NIH HHS; HL-51971/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
103745-39-7/fasudil; 11128-99-7/Angiotensin II; 69PN84IO1A/Enalapril; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; EC 2.7.11.1/rho-Associated Kinases
Comments/Corrections

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