Vasodilator effects of sulforaphane in cerebral circulation: A critical role of endogenously produced hydrogen sulfide and arteriolar smooth muscle KATP and BK channels in the brain.
J Cereb Blood Flow Metab
; 40(10): 1987-1996, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-31594422
ABSTRACT
We investigated the effects of sulforaphane (SFN), an isothiocyanate from cruciferous vegetables, in the regulation of cerebral blood flow using cranial windows in newborn pigs. SFN administered topically (10 µM-1 mM) or systemically (0.4 mg/kg ip) caused immediate and sustained dilation of pial arterioles concomitantly with elevated H2S in periarachnoid cortical cerebrospinal fluid. H2S is a potent vasodilator of cerebral arterioles. SFN is not a H2S donor but it acts via stimulating H2S generation in the brain catalyzed by cystathionine γ-lyase (CSE) and cystathionine ß-synthase (CBS). CSE/CBS inhibitors propargylglycine, ß-cyano-L-alanine, and aminooxyacetic acid blocked brain H2S generation and cerebral vasodilation caused by SFN. The SFN-elicited vasodilation requires activation of potassium channels in cerebral arterioles. The inhibitors of KATP and BK channels glibenclamide, paxilline, and iberiotoxin blocked the vasodilator effects of topical and systemic SFN, supporting the concept that H2S is the mediator of the vasodilator properties of SFN in cerebral circulation. Overall, we provide first evidence that SFN is a brain permeable compound that increases cerebral blood flow via a non-genomic mechanism that is mediated via activation of CSE/CBS-catalyzed H2S formation in neurovascular cells followed by H2S-induced activation of KATP and BK channels in arteriolar smooth muscle.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arterioles
/
Vasodilator Agents
/
Cerebrovascular Circulation
/
Isothiocyanates
/
Large-Conductance Calcium-Activated Potassium Channels
/
KATP Channels
/
Hydrogen Sulfide
/
Muscle, Smooth, Vascular
Limits:
Animals
Language:
En
Journal:
J Cereb Blood Flow Metab
Year:
2020
Document type:
Article
Affiliation country:
Estados Unidos