Document Detail

Angiotensin-converting enzyme inhibition during development alters calcium regulation in adult hypertensive rats.
MedLine Citation:
PMID:  7505333     Owner:  NLM     Status:  MEDLINE    
Studies have shown that angiotensin-converting enzyme (ACE) inhibitor treatment in young genetically hypertensive rats prevents the full expression of blood pressure and vascular abnormalities in the adult. This model provides unique conditions with which to study the pathogenesis of altered Ca++ regulation. Normotensive (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) received at 6 to 10 weeks of age either ACE inhibitor (ramipril), hydralazine/hydrochlorothiazide or no treatment. At 17 weeks of age, rats were anesthetized, and vascular tissue was excised. Thoracic aorta challenged with 20 mM caffeine in Ca(++)-free buffer produced a phasic contractile response. The magnitude of this phasic response was used as a measure of Ca++ released from intracellular stores; a direct correlation between this phasic response and systolic blood pressure was observed. A concentration-response curve to Bay K8644 was performed on carotid arteries; a direct correlation of force development to Bay K8644 and systolic blood pressure was observed. All WKY groups showed lower blood pressure and force development in response to Bay K8644 than did SHRSP. Treatment with ramipril reduced blood pressure and force development in response to Bay K8644 in adult SHRSP, although not to levels of WKY rats, whereas WKY rats were unaffected by treatment. These data support the hypothesis that contractile responses to Bay K8644 in carotid arteries and caffeine in aorta parallel changes in systolic blood pressure. We conclude that alteration of Ca++ regulation in hypertension is directly related to elevated blood pressure and mediated by an angiotensin II-sensitive mechanism during development.
O Traub; R C Webb
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  267     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1993 Dec 
Date Detail:
Created Date:  1994-01-27     Completed Date:  1994-01-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1503-8     Citation Subset:  IM    
Department of Physiology, University of Michigan, Ann Arbor.
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MeSH Terms
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Blood Pressure / drug effects,  physiology
Caffeine / pharmacology
Calcium / metabolism,  physiology*
Calcium Channels / drug effects,  physiology
Cell Membrane / metabolism,  physiology
Disease Models, Animal
Hydralazine / pharmacology
Hydrochlorothiazide / pharmacology
Hypertension / drug therapy,  enzymology,  physiopathology*
Muscle Contraction / drug effects,  physiology
Muscle, Smooth, Vascular / drug effects,  metabolism,  physiology
Ramipril / pharmacology
Rats, Inbred SHR
Rats, Inbred WKY
Sarcoplasmic Reticulum / metabolism,  physiology
Grant Support
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Calcium Channels; 58-08-2/Caffeine; 58-93-5/Hydrochlorothiazide; 71145-03-4/3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; 7440-70-2/Calcium; 86-54-4/Hydralazine; 87333-19-5/Ramipril

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