Blood pressure and small arteries in DOCA-salt-treated genetically AVP-deficient rats - Role of endothelin

Hypertension is associated with structural and mechanical abnormalities of resistance arteries. We have recently reported that vasopressin may be invo lved in the blood pressure elevation and remodeling of resistance arteries in deoxycorticosterone acetate (DOCA)-salt hypertension, perhaps by modulat ing vascular endothelin-1 expression. We tested this hypothesis further by examining DOCA-salt hypertension in homozygous vasopressin-deficient Brattl eboro (BB) rats in comparison with Long-Evans (LE; control) rats. Mesenteri c resistance arteries (lumen <300 mu m) were studied on pressurized myograp hs. After 5 weeks, systolic blood pressure was greater in LE DOCA-salt-trea ted rats (189+/-5 mm Hg) compared with uniephrectomized (UNx) LE control ra ts (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 D OCA-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), Resistanc e 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 compa red with LE-UNx rats. Isobaric stiffness was unaltered in resistance arteri es 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 th e absence of endogenous vasopressin, ie, in homozygous di/di BB rats, faile d to alter vascular structure or wall component stiffness and resulted in a lesser degree of blood pressure elevation. Reverse transcription-polymeras e chain reaction analysis revealed that DOCA-salt treatment enhanced endoth elin 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 stru cture and mechanics, as well as blood pressure, in DOCA-salt-induced hypert ension. Moreover, these effects of vasopressin are in part mediated by enha ncement of endothelin expression.