title: Inhibition of NO biosynthesis, but not elevated blood pressure, reduces angiogenesis in rat models of secondary hypertension.
abstract: Arterial hypertension (AH) is characterized by reduced nitric oxide (NO) biosynthesis, vasoconstriction, and reduced microvascular density. In this study we asked whether AH also reduces the number of microvessels by impairing angiogenesis. AH was induced in Dahl salt-sensitive rats (DSS) with a salt diet and in Wistar-Kyoto rats by inhibiting NO formation with Nomega-nitro-L-arginine (NNA). Three weeks after induction of AH, two wound chambers containing collagen I (Vitrogen) were sutured into the mesenteric cavity of each animal. After additional 14 days, wound chamber neovascularization and the extent of vascularized connective tissue ingrowth were quantified. In NNA-induced AH, the number of newly formed vessels and the ingrowth of vascularized connective tissue into the wound chamber decreased as compared to controls. However, the number of newly formed vessels and the ingrowth of vascularized connective tissue did not change with increasing blood pressure in salt-fed DSS rats as compared to those fed a normal diet. Inhibition of NO biosynthesis, but not necessarily elevating blood pressure, reduces angiogenesis. Microvascular rarefaction in AH may be partially due to reduced angiogenesis because of impaired NO biosynthesis.
authors.affiliation: Department of Research, University Hospital, Basel, Switzerland.
authors.forename: Fabrice N
authors.initials: FN
authors.lastname: Kiefer
authors.forename: Heidi
authors.initials: H
authors.lastname: Misteli
authors.forename: Nabil
authors.initials: N
authors.lastname: Kalak
authors.forename: Karin
authors.initials: K
authors.lastname: Tschudin
authors.forename: Jürgen
authors.initials: J
authors.lastname: Fingerle
authors.forename: Maaike
authors.initials: M
authors.lastname: Van der Kooij
authors.forename: Michael
authors.initials: M
authors.lastname: Stumm
authors.forename: Lazar T
authors.initials: LT
authors.lastname: Sumanovski
authors.forename: Cornel C
authors.initials: CC
authors.lastname: Sieber
authors.forename: Edouard J
authors.initials: EJ
authors.lastname: Battegay
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology*; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000096:biosynthesis*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D011921:Rats, Inbred WKY; D012965:Sodium Chloride / Q000008:administration & dosage
chemical_list: D019335:Nitroarginine; D009569:Nitric Oxide; D012965:Sodium Chloride