Signal transduction in spontaneous myogenic tone in isolated arterioles from rat skeletal muscle.

Abstract:

OBJECTIVE:The mechanism of spontaneous myogenic tone was investigated in isolated arteriolar segments. METHODS:Arterioles were isolated from rat cremaster muscle. Segments were endothelium-denuded and mounted in a pressure myograph at 75 mmHg. Under this condition, segments spontaneously constricted from a passive diameter of 167 +/- 3 to 82 +/- 4 microns (n = 41). The effects of several inhibitors were tested on the maintenance of myogenic tone. RESULTS:Gadolinium (10(-6)-10(-4) M), a putative inhibitor of stretch-activated cation channels, was ineffective. The phospholipase C (PLC) inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC) induced a dose-dependent inhibition of tone. NCDC inhibited phenylephrine- (10(-6) M), but not potassium buffer-induced (100 mM) constriction. The protein kinase C (PKC) inhibitors staurosporine, chelerythrine and calphostin C inhibited myogenic tone in a concentration-dependent manner. At an intermediate concentration, calphostin C selectively inhibited phenylephrine-induced constriction. However, all PKC inhibitors abolished responses to phenylephrine and potassium buffer at higher concentrations. The cytochrome P450 inhibitor 17-ODYA (0.3-3 x 10(-6) M) did not inhibit myogenic tone. CONCLUSIONS:No evidence was found for a role of gadolinium-sensitive, stretch-activated cation channels or cytochrome P450 metabolites. On the other hand, both PLC and PKC contribute to the maintenance of myogenic tone.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Bakker EN,Kerkhof CJ,Sipkema P

doi

10.1016/s0008-6363(98)00161-8

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

229-36

issue

1

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(98)00161-8

journal_volume

41

pub_type

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