title: Blood pressure and small arteries in DOCA-salt-treated genetically AVP-deficient rats: role of endothelin.
abstract: Hypertension is associated with structural and mechanical abnormalities of resistance arteries. We have recently reported that vasopressin may be involved in the blood pressure elevation and remodeling of resistance arteries in deoxycorticosterone acetate (DOCA)-salt hypertension, perhaps by modulating vascular endothelin-1 expression. We tested this hypothesis further by examining DOCA-salt hypertension in homozygous vasopressin-deficient Brattleboro (BB) rats in comparison with Long-Evans (LE; control) rats. Mesenteric resistance arteries (lumen <300 microm) were studied on pressurized myographs. After 5 weeks, systolic blood pressure was greater in LE DOCA-salt-treated rats (189+/-5 mm Hg) compared with uniephrectomized (UNx) LE control rats (117+/-4 mm Hg; P<0.01). The increase in blood pressure induced by DOCA-salt treatment was attenuated in vasopressin-deficient rats, such that BB DOCA-salt-treated rats exhibited only a slight elevation of blood pressure (134+/-6 mm Hg) compared with BB-UNx rats (111+/-4 mm Hg; P<0.05). Resistance arteries in LE DOCA-salt-treated rats had a smaller lumen diameter and a larger media width, media cross-sectional area, and media-lumen ratio compared with LE-UNx rats. Isobaric stiffness was unaltered in resistance arteries from LE DOCA-salt-treated rats, despite stiffening of the arterial wall components as indicated by a significant increase in the slope of the media stress-incremental elastic modulus relationship. DOCA-salt treatment in the absence of endogenous vasopressin, ie, in homozygous di/di BB rats, failed to alter vascular structure or wall component stiffness and resulted in a lesser degree of blood pressure elevation. Reverse transcription-polymerase chain reaction analysis revealed that DOCA-salt treatment enhanced endothelin gene expression in LE rats but failed to do so in BB rats. These data indicate that vasopressin plays a critical role in modulating vascular structure and mechanics, as well as blood pressure, in DOCA-salt-induced hypertension. Moreover, these effects of vasopressin are in part mediated by enhancement of endothelin expression.
authors.affiliation: MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Quebec, Canada.
authors.forename: H D
authors.initials: HD
authors.lastname: Intengan
authors.forename: J B
authors.initials: JB
authors.lastname: Park
authors.forename: E L
authors.initials: EL
authors.lastname: Schiffrin
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D003900:Desoxycorticosterone; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D014655:Vascular Resistance / Q000502:physiology*; D014667:Vasopressins / Q000172:deficiency* / Q000235:genetics
chemical_list: D019332:Endothelin-1; D014667:Vasopressins; D003900:Desoxycorticosterone