Augmentation index and central aortic stiffness in middle-aged to elderly individuals.

BACKGROUND: Increased aortic stiffness contributes to systolic hypertension and increased cardiovascular risk. The augmentation index (AI), ie, the percentage of central pulse pressure attributed to reflected wave overlap in systole, was proposed as a noninvasive indicator of increased arterial stiffness. We evaluated this hypothesis by investigating relations between AI and other direct measures of aortic stiffness. METHODS: Tonometric carotid- and femoral-pressure waveforms, Doppler aortic flow, and aortic-root diameter were assessed in 123 individuals with uncomplicated systolic hypertension and 29 controls of comparable age and sex. Carotid-femoral pulse-wave velocity (PWV) was assessed from the carotid-femoral time delay and body-surface measurements. Aortic PWV was assessed from the ratio of the upstroke of carotid pressure and aortic flow velocity and was used to calculate proximal aortic compliance as [aortic area]/[1.06 x (aortic PWV)(2)]. RESULTS: Partial correlations (adjusted for age, sex, presence of hypertension, height, weight, and systolic ejection period) showed no association between AI and carotid-femoral PWV (R = -0.05, P = .54). The AI was significantly though weakly related directly with aortic compliance (R = 0.21, P = .012) and inversely with aortic PWV (R = -0.198, P = .017). However, higher stiffness (lower compliance and higher PWV) was associated with lower AI. CONCLUSIONS: Increased AI is not a reliable surrogate for increased aortic stiffness. Decreasing AI with decreasing compliance (increasing aortic stiffness) may be attributable to impedance matching and reduced wave reflection at the interface between the aorta and the muscular arteries.

Prior exposure to chronic stress and MDMA potentiates mesoaccumbens dopamine release mediated by the 5-HT(1B) receptor.

(+) 3,4,-Methylenedioxymethamphetamine (MDMA) is an abused drug that acutely releases serotonin (5-HT) and dopamine (DA) but produces long-term damage to 5-HT terminals. MDMA-induced DA release has been shown to be dampened by 5-HT. Although stress also activates the mesolimbic DA pathway, it is unknown if chronic stress after exposure to neurotoxic doses of MDMA will augment MDMA-induced DA release in the nucleus accumbens shell (NAcc(sh)). Rats were pretreated with MDMA (10 mg/kg x 4, intraperitoneal (i.p.)). After 7 days, rats were subjected to 10 days of chronic unpredictable stress. DA release in the NAcc(sh) and 5-HT in the ventral tegmental area (VTA) were measured after a challenge injection of MDMA (5 mg/kg, i.p.). The combination of pretreatment with MDMA+stress decreased basal concentrations of 5-HT in the VTA and DA in the NAcc(sh) and enhanced MDMA-stimulated DA release in the NAcc(sh). Pretreatment with MDMA or stress alone blunted MDMA-induced 5-HT release in the VTA. The augmentation of MDMA-induced DA release in rats pretreated with MDMA+chronic stress was attenuated by perfusion of the 5-HT(1B) antagonist, GR127935 into the VTA before the MDMA challenge injection. These results suggest that prior exposure to both MDMA and stress can produce a long-term augmentation in mesolimbic DA transmission and enhanced drug abuse vulnerability that is mediated, in part, by the 5-HT(1B) receptor in the VTA.