Exaggerated Cardiovascular Stress Responses and Impaired β-Adrenergic–Mediated Pressor Recovery in Obese Zucker Rats

Gerard D’Angelo, James D. Mintz, John E. Tidwell, Ann M. Schreihofer,David M. Pollock, David W. Stepp.Hypertension. 2006;48:1109-1115.Obesity is a major risk factor for development of metabolic disorders. Besides the increased risk for metabolic disorders there increase in the pressor response that results from mental, physical and acute stress. Since α and β adrenergic receptors are important for determining vascular tone, changes in either receptor expression or sensitivity to norepinephrine or epinephrine. In a previous study this laboratory demonstrated that pressor responses to ganglionic blockade was not different between obese and lean zucker rats. They also demonstrated that isolated mesenteric resistance arteries responses to exogenous norepinephrine is attenuated when compared to lean zucker rats. They concluded from this data that there is elevated peripheral vascular resistance. Furthermore, it may be due suppressed β-adrenergic-mediated vasodilation. In this study they hypothesized that pressor responses to environmental stressors would be greater in the obese versus the lean zucker rats. The elevated pressor response in the obese zucker will be most likely due to attenuated vasodilation as a result of impaired β- adrenergic mechanisms. Obese and lean zucker rats ( and LZR, respectively)were implanted with telemetry probes in order to record blood pressure under conscience conditions. Following recovery animals were brought to a soundproof room and then the animals were put into restrainers and a baseline blood pressure and heart rate were monitored for fifteen minutes prior to the air jet stress. In a separate group of obese and lean zucker rats, following the fifteen minute control period propranolol was administered and then the air jet stress was initiated. They also instrument animals so they could determine blow flow to the mesenteric arteries and aorta.They also looked at cardiac output along with blood glucose, plasma levels of cholesterol and triglycerides. They also looked at thyroid hormones T3/T4.They found that OZR had higher baseline BP and HR variability. In response to stress the OZR the area under the curve (AUC) for blood pressure was significantly higher in obese untreated when compared to the LZR. the AUC 20 minutes post stress was significatly greater in the OZR when compared to LZR. There was also a significant increase in AUC following treatment with propranolol in the LZR. They further analyzed the role of β-adrenergic receptors following ganglionic blockade. prior to ganglionic blockade, β-adrenergic receptor blockade resulted concentration dependent decreases in MAP in both groups, however the OZR had attentuated response when compared to LZR. Following ganglionic blockade resulted in a similar trend. They also looked at hindlimb and mesenteric conductance. There were no differences in hindlimb conductance between OZR and LZR ganglionic blockade in response to β- adrenergic blockade. As for mesenteric conductance both group exhibit increases in conductance, however only at 0.05,0.1, 0.5 μmoles of isoproterenol is there an attenuation in the OZR response when compared to LZR. As for cardiac output, there is an increase in response to isoproterenol in both group however the OZR had attenuated changes in CO at 0.05 and 0.5 μmoles. These data suggest that Obesity may lead to attenuated β- adrenergic mediated vasodilation. This β- adrenergic mediated vasodilation is playing an important role in the recovery period for stress.-MD