Role of voltage-sensitive calcium-channels in nitric oxide-mediated vasodilation in spontaneously hypertensive rats.
This study demonstrates that the vasodilator potencies of nitric oxide (NO) donors such as sodium nitroprusside are increased in conscious Spontaneously Hypertensive (SH) as compared to Wistar Kyoto (WKY) rats. For example, the NO donors do not dilate hindlimb resistance arteries in WKY rats whereas they elicit pronounced vasodilator responses in SH rats. This study also demonstrates that the NO-mediated vasodilator responses in WKY and SH rats were markedly diminished after blockade of voltage-sensitive Ca2+-channels (CaVS2+-channels) with nifedipine, diltiazem or verapamil. These findings suggest that NO dilates resistance arteries in vivo via direct and/or hyperpolarization-induced closure of CaVS2+-channels and that the increased potency of NO in SH rats may be due to the augmented CaVS2+-channel activity reported in this strain.
Lewis
Stephen J
SJ
Department of Pharmacology and Physiology, University of Georgia, Athens, GA 30602-7389, USA. slewis@vet.uga.edu
Bhopatkar
Monica Y
MY
Walton
Tina M
TM
Bates
James N
JN
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D006614:Hindlimb; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D026403:S-Nitrosothiols / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
C105785:1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D006834:Hydrazines; D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D003545:Cysteine