Linked Life Data

9931130

Source:http://linkedlifedata.com/resource/pubmed/id/9931130

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1 Pt 2
pubmed:dateCreated
1999-2-26
pubmed:abstractText
Intracellular Ca2+ ([Ca2+]i) homeostasis regulates vascular smooth muscle tone, and alteration in [Ca2+]i handling is associated with the development and establishment of hypertension. We have previously established in the spontaneously hypertensive rat (SHR) that virally mediated delivery of angiotensin II type 1 receptor antisense (AT1R-AS) prevents the development of high blood pressure and some pathophysiology associated with hypertension for 120 days. In light of this, our objectives in this study were to determine whether AT1R-AS gene therapy (1) could have a longer duration in the prevention of hypertension and (2) would attenuate the alterations in renal vascular Ca2+ homeostasis and therefore vasoconstriction, characteristics of hypertension. Intracardiac delivery of AT1R-AS in neonates prevented the development of hypertension in SHR for at least 210 days. At this time, untreated SHR renal resistance arterioles showed a significantly enhanced contractile response to KCl and angiotensin II (Ang II) when compared with normotensive Wistar-Kyoto rats. In addition, L-type Ca2+ current density and Ang II-dependent increases in [Ca2+]i were significantly increased in cells dissociated from renal resistance arterioles of the untreated SHR. AT1R-AS treatment prevented all of the above vascular alterations associated with the hypertensive state in SHR. Finally, Western blot analysis of L-type Ca2+ channel (alpha1C) protein levels in renal resistance arterioles of untreated SHR showed no significant difference when compared with control. These results are novel and demonstrate that viral-mediated delivery of AT1R-AS not only attenuates the development of hypertension on a long-term basis but prevents changes in renal vascular Ca2+ homeostasis associated with the disease.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0194-911X
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
360-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9931130-Angiotensin II, pubmed-meshheading:9931130-Animals, pubmed-meshheading:9931130-Arterioles, pubmed-meshheading:9931130-Blood Pressure, pubmed-meshheading:9931130-Calcium, pubmed-meshheading:9931130-Cells, Cultured, pubmed-meshheading:9931130-DNA, Antisense, pubmed-meshheading:9931130-Gene Therapy, pubmed-meshheading:9931130-Homeostasis, pubmed-meshheading:9931130-Hypertension, pubmed-meshheading:9931130-Male, pubmed-meshheading:9931130-Membrane Potentials, pubmed-meshheading:9931130-Muscle, Smooth, Vascular, pubmed-meshheading:9931130-Patch-Clamp Techniques, pubmed-meshheading:9931130-Potassium Chloride, pubmed-meshheading:9931130-Rats, pubmed-meshheading:9931130-Rats, Inbred SHR, pubmed-meshheading:9931130-Rats, Inbred WKY, pubmed-meshheading:9931130-Receptor, Angiotensin, Type 1, pubmed-meshheading:9931130-Receptor, Angiotensin, Type 2, pubmed-meshheading:9931130-Receptors, Angiotensin, pubmed-meshheading:9931130-Renal Circulation, pubmed-meshheading:9931130-Vascular Resistance, pubmed-meshheading:9931130-Vasoconstriction
pubmed:year
1999
pubmed:articleTitle
Angiotensin II type 1 receptor antisense gene therapy prevents altered renal vascular calcium homeostasis in hypertension.
pubmed:affiliation
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610, USA. Gelband@phys.med.ufl.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Retracted Publication, Research Support, Non-U.S. Gov't