No abstract

We investigated the effects of diet-induced obesity on glucose metabolism in two strains of mice, C57BL/6J and A/J. Twenty animals from each strain received ad libitum exposure to a high-fat high-simple-carbohydrate diet or standard Purina Rodent Chow for 6 mo. Exposure to the high-fat, high-simple-carbohydrate, low-fiber diet produced obesity in both A/J and C57BL/6J mice. Whereas obesity was associated with only moderate glucose intolerance and insulin resistance in A/J mice, obese C57BL/6J mice showed clear-cut diabetes with fasting blood glucose levels of greater than 240 mg/dl and blood insulin levels of greater than 150 microU/ml. C57BL/6J mice showed larger glycemic responses to stress and epinephrine in the lean state than AJ mice, and these responses were exaggerated by obesity. These data suggest that the C57BL/6J mouse carries a genetic predisposition to develop non-insulin-dependent (type II) diabetes. Furthermore, altered glycemic response to adrenergic stimulation may be a biologic marker for this genetic predisposition to develop type II diabetes.

In three experiments involving young adult males, beta‐adrenergic influences on heart rate and carotid dP/dt were evaluated as a function of the degree of individual control over stressful events. Beta‐adrenergic effects were more pronounced under conditions in which the subjects were either led to believe they had control or where some control was actually provided, i.e., a shock avoidance task. Beta‐adrenergic influences were either minimal or rapidly dissipated under conditions where no control was possible, i.e., the cold pressor, a pornographic film, inescapable shocks, or conditions which provided ready mastery of the task. Where beta‐adrenergic effects were maximal, systolic blood pressure was more appreciably elevated while diastolic blood pressure was less elevated than when beta‐adrenergic effects were minimal. A pharmacological blocking agent (propranolol) was used in one experiment to specify the extent the various cardiovascular changes were influenced by beta‐adrenergic activity. The results are discussed with respect to issues concerning stimulus parameters, blood pressure control mechanisms, individual differences in cardiovascular reactivity, and some methodological problems of the current study.

Resting blood pressure is inversely correlated with acute pain sensitivity in healthy normotensives. This study tested: (1) whether endogenous opioid activity is necessary for this adaptive relationship to occur, (2) whether this relationship is altered in chronic low back pain (LBP), and (3) whether endogenous opioid dysfunction underlies any such alterations. Fifty-one pain-free normotensives and 44 normotensive chronic LBP sufferers received opioid blockade (8 mg naloxone i.v.) or placebo blockade (saline) in randomized, counterbalanced order in separate sessions. During each session, subjects participated in a 1-min finger pressure (FP) pain task followed by an ischemic (ISC) forearm pain task. Among pain-free normotensives, elevated resting systolic (SBP) and diastolic (DBP) blood pressure were associated with significantly higher ISC pain thresholds (P values <0.05). Elevated SBP was also associated with significantly lower FP pain ratings (P<0.05). Opioid blockade had no significant effect on the BP-pain relationships detected (P values >0.10). In combined groups analyses, a significant subject typexSBP interaction (P<0.005) was found on ISC pain threshold: elevated SBP was associated with higher pain threshold in pain-free controls, but with lower pain threshold in LBP subjects. Although subject typexBP interactions on FP and ISC pain ratings were not significant, inclusion of LBP subjects in these analyses resulted in the overall relationship between BP and pain sensitivity becoming positive (P values <0.05). Opioid blockade exerted no significant main or interaction effects in these combined groups analyses (p values >0.10). Higher DBP was associated with greater clinical pain intensity among the LBP subjects (P<0.001). Overall, these results suggest: (1) endogenous opioids do not mediate the inverse relationship between resting blood pressure and acute pain sensitivity in pain-free normotensives; (2) the BP-pain sensitivity relationship is altered in chronic pain, suggesting dysfunction in pain regulatory systems, and (3) these alterations are not related to opioid dysfunction.

Hypertension has been found to be related to decreased sensitivity to painful stimuli. The current study explored whether this relationship extends into the normotensive range of blood pressures. Resting blood pressures were assessed in 60 male normotensives. Subjects then underwent a 1 min finger pressure pain stimulation trial. Pain ratings were inversely related to resting systolic blood pressure. This relationship was unrelated to emotional state or coping styles. Multiple regression analyses indicated that over one-third of the variance in pain ratings can be accounted for by resting blood pressure, coping style, and emotional state.