title: Sustained hypertension despite endothelial-specific eNOS rescue in eNOS-deficient mice.
abstract: The aim of the study was to evaluate the possible contribution of non-endothelial eNOS to the regulation of blood pressure (BP). To accomplish this, a double transgenic strain expressing eNOS exclusively in the vascular endothelium (eNOS-Tg/KO) has been generated by endothelial-specific targeting of bovine eNOS in eNOS-deficient mice (eNOS-KO). Expression of eNOS was evaluated in aorta, myocardium, kidney, brain stem and skeletal muscle. Organ bath studies revealed a complete normalization of aortic reactivity to acetylcholine, phenylephrine and the NO-donors in eNOS-Tg/KO. Function of eNOS in resistance arteries was demonstrated by acute i.v. infusion of acetylcholine and the NOS-inhibitor L-NAME. Acetylcholine decreased mean arterial pressure in all strains but eNOS-KO responded significantly less sensitive as compared eNOS-Tg/KO and C57BL/6. Likewise, acute i.v. L-NAME application elevated mean arterial pressure in C57BL/6 and eNOS-Tg/KO, but not in eNOS-KO. In striking contrast to these findings, mean, systolic and diastolic BP in eNOS-Tg/KO remained significantly elevated and was similar to values of eNOS-KO. Chronic oral treatment with L-NAME increased BP to the level of eNOS-KO only in C57BL/6, but had no effect on hypertension in eNOS-KO and eNOS-Tg/KO. Taken together, functional reconstitution of eNOS in the vasculature of eNOS-KO not even partially lowered BP. These data suggest that the activity of eNOS expressed in non-vascular tissue might play a role in physiologic BP regulation.
authors: Institute of Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: Tatsiana
authors: T
authors: Suvorava
authors: Department of Nephrology, University Hospital, Heinrich-Heine-University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: Johannes
authors: J
authors: Stegbauer
authors: Department of Nephrology, University Hospital, Heinrich-Heine-University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: Manuel
authors: M
authors: Thieme
authors: Institute of Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: Stephanie
authors: S
authors: Pick
authors: Department of Nephrology, University Hospital, Heinrich-Heine-University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: Sebastian
authors: S
authors: Friedrich
authors: Department of Nephrology, University Hospital, Heinrich-Heine-University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: Lars C
authors: LC
authors: Rump
authors: Institute of Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: Thomas
authors: T
authors: Hohlfeld
authors: Institute of Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Universitätsstr. 1, 40225 Düsseldorf, Germany. Electronic address: kojda@uni-duesseldorf.de.
authors: Georg
authors: G
authors: Kojda
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001919:Bradycardia / Q000150:complications; D002417:Cattle; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism
chemical_list: D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: Blood pressure; Endothelium; Transgenic mice; eNOS