Exaggerated blood pressure response to fasudil or nifedipine in hypertensive Ren-2 transgenic rats: role of altered baroreflex
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00504437" target="_blank" >RIV/67985823:_____/19:00504437 - isvavai.cz</a>
Alternative codes found
RIV/00023001:_____/19:00077659
Result on the web
<a href="https://www.nature.com/articles/s41440-018-0146-x" target="_blank" >https://www.nature.com/articles/s41440-018-0146-x</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41440-018-0146-x" target="_blank" >10.1038/s41440-018-0146-x</a>
Alternative languages
Result language
angličtina
Original language name
Exaggerated blood pressure response to fasudil or nifedipine in hypertensive Ren-2 transgenic rats: role of altered baroreflex
Original language description
Basal calcium sensitization is decreased in spontaneously hypertensive rats, although their blood pressure (BP) response to acute Rho-kinase inhibition is enhanced. Using fasudil (Rho-kinase inhibitor) or nifedipine (L-VDCC blocker), we evaluated the contribution of calcium sensitization and calcium entry to BP maintenance in hypertensive transgenic Ren-2 rats (TGR) focusing on the influence of major vasoactive systems and/or baroreflex efficiency on BP responses to these two drugs. Homozygous TGR and normotensive Hannover Sprague-Dawley (HanSD) control rats aged 5, 11, or 22 weeks were used. The acute BP-lowering effects of fasudil or nifedipine were studied in intact rats, nitric oxide-deficient L-NAME-pretreated rats and rats subjected to combined blockade of the renin-angiotensin system (RAS), sympathetic nervous system (SNS) and nitric oxide synthase (NOS). Fasudil- or nifedipine-induced BP reduction increased during hypertension development in TGR. By contrast, the nifedipine-induced BP response decreased, whereas the fasudil-induced BP response increased with age in HanSD controls. Our data indicated a major contribution of nifedipine-sensitive calcium entry and relative attenuation of calcium sensitization in hypertensive rats compared with normotensive controls. The BP responses to fasudil or nifedipine were enhanced by NOS inhibition and combined blockade in normotensive HanSD rats but not in hypertensive TGR. In conclusion, calcium sensitization is attenuated by endogenous nitric oxide in normotensive HanSD rats but not in hypertensive TGR. Moreover, BP reduction elicited by acute Rho-kinase inhibition is partially compensated by enhanced sympathetic vasoconstriction. The decreased compensation in hypertensive rats with impaired baroreflex efficiency explains their greater BP response to fasudil than in normotensive animals.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
<a href="/en/project/NV15-25396A" target="_blank" >NV15-25396A: Central and peripheral modulation of vascular tone and sodium excretion: the role of brain and kidney in pathophysiology of hypertension</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Hypertension Research
ISSN
0916-9636
e-ISSN
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Volume of the periodical
42
Issue of the periodical within the volume
2
Country of publishing house
JP - JAPAN
Number of pages
10
Pages from-to
145-154
UT code for WoS article
000457729000004
EID of the result in the Scopus database
2-s2.0-85058049575