Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24597655
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Beneficial effects of diminished production of hydrogen sulfide or carbon
monoxide on hypertension and renal injury induced by NO withdrawal
#MMPMID24597655
Wesseling S
; Fledderus JO
; Verhaar MC
; Joles JA
Br J Pharmacol
2015[Mar]; 172
(6
): 1607-19
PMID24597655
show ga
BACKGROUND AND PURPOSE: Whether NO, carbon monoxide (CO) and hydrogen sulfide (H2
S) compensate for each other when one or more is depleted is unclear. Inhibiting
NOS causes hypertension and kidney injury. Both global depletion of H2 S by
cystathionine ?-lyase (CSE) gene deletion and low levels of exogenous H2 S cause
hypertension. Inhibiting CO-producing enzyme haeme oxygenase-1 (HO-1) makes
rodents hypersensitive to hypertensive stimuli. We hypothesized that combined
inhibition of NOS and HO-1 exacerbates hypertension and renal injury, but how
combined inhibition of NOS and CSE affect hypertension and renal injury was
unclear. EXPERIMENTAL APPROACH: Rats were treated with inhibitors of NOS
(L-nitroarginine; LNNA), CSE (DL-propargylglycine; PAG), or HO-1 (tin
protoporphyrin; SnPP) singly for 1 or 4 weeks or in combinations for 4 weeks. KEY
RESULTS: LNNA always reduced NO, decreased H2 S and increased CO after 4 weeks.
PAG abolished H2 S, always enhanced CO and reduced NO, but not when used in
combination with other inhibitors. SnPP always increased NO, enhanced H2 S and
inhibited CO after 1 week. Rats treated with LNNA, but not PAG and SnPP, rapidly
developed hypertension followed by renal dysfunction. LNNA-induced hypertension
was ameliorated and renal dysfunction prevented by all additional treatments.
Renal HO-1 expression was increased by LNNA in injured tubules and increased in
all tubules by all other treatments. CONCLUSIONS AND IMPLICATIONS: The
amelioration of LNNA-induced hypertension and renal injury by additional
inhibition of H2 S and/or CO-producing enzymes appeared to be associated with
secondary increases in renal CO or NO production.
free
free
free
