Effect of NO synthase inhibition on cardiovascular circadian rhythms in wild-type and eNOS-knock-out mice.
Cardiovascular functions (blood pressure [BP], heart rate [HR]) were radiotelemetrically studied in endothelial nitric oxide synthase (NOS) knock-out mice (eNOS-/-) and their wild type C57BL/6 (WT) controls. Studies were performed with and without inhibition of the NOS with the non-specific inhibitor N(omega)-Nitro-L-Arginin-Methylester (L-NAME). Six eNOS-/-and five WT mice, kept under a light:dark schedule of 12:12 h (lights on 07:00 h), were treated with L-NAME in tap water containing different concentrations (94, 282, and 940 mg/kg) each for three days. Under control conditions, the eNOS-/-mice are mildly hypertensive in comparison to WT. L-NAME increased systolic [SBP] and diastolic [DBP] blood pressures in WT mice to the levels of eNOS-/-mice after two days of L-NAME application with no dose-dependency, whereas L-NAME had no effects on SBP and DBP in eNOS-/-mice. In neither mouse strain were the circadian rhythms in BP and HR affected by drug treatment. The similarity of the 24 h BP profiles in eNOS-/-and L-NAME-treated WT mice support the notion that only the enothelial NOS and not other NOS isoenzymes are of importance for hypertension in the knock-out mouse strain.
Lemmer
Bjõrn
B
Institute of Experimental and Clinical Pharmacology and Toxicology, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
Arraj
Mahran
M
D000818:Animals; D001794:Blood Pressure; D002319:Cardiovascular System; D002940:Circadian Rhythm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000175:diagnosis / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D011846:Radio Waves; D013686:Telemetry; D013997:Time Factors
D004791:Enzyme Inhibitors; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019331:NG-Nitroarginine Methyl Ester