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Background: Coronary vasomotor dysfunction is an important mechanism for angina in patients with unobstructed coronary arteries.Objectives: The purpose of this study was to determine sex differences in the prevalence and clinical presentation of vasomotor dysfunction in a European population and to examine sex differences in the dose of acetylcholine leading to a positive acetylcholine provocation test (ACH test).Methods: Between 2007 and 2014, we included 1,379 consecutive patients with stable angina, unobstructed coronaries and ACH test performed for epicardial vasospasm or coronary microvascular dysfunction (CMD) due to microvascular spasm. The predictive value of sex, risk factors, symptoms, and noninvasive test results was analyzed by means of logistic regression.Results: The mean patient age was 62 years, and 42% were male. There were 813 patients (59%) with a pathological ACH test, 33% for CMD and 26% for epicardial vasospasm. A pathological test was more common in females (70% vs. 43%; p < 0.001). In a multivariable logistic regression model the sex difference was statistically significant with a female-male odds ratio for CMD and epicardial vasospasm of 4.2 (95% confidence interval: 3.1 to 5.5; p < 0.001) and 2.3 (95% confidence interval: 1.7 to 3.1; p < 0.001), respectively. Effort-related symptoms, but neither risk factors nor noninvasive stress tests, contributed to predicting a pathological test. Female patients were more sensitive to acetylcholine with vasomotor dysfunction occurring at lower ACH doses compared with male patients.Conclusions: Vasomotor dysfunction is frequent in patients with angina and unobstructed coronaries in a European population. Female patients have a higher prevalence of vasomotor dysfunction (especially CMD) compared with male patients. A pathological ACH test was observed at lower ACH doses in women compared with men. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have demonstrated that amyloid-β1–42 (Aβ1–42) binds to the nicotinergic α7 acetylcholine receptor (α7 nAChR) and that the application of Aβ1–42 to cells inhibits the function of the α7 nAChR. The in vivo consequences of the pharmacological activation of the α7 nAChR have not been examined. The aim of this study has been to evaluate the efficacy of α7 nAChR modulators in transgene mice that overexpress human amyloid precursor protein and accumulate Aβ1–40 and Aβ1–42. In accordance with observations in human Alzheimer tissues, we show here through the use of co-immunoprecipitation that human Aβ-immunoreactive peptides bind to mice α7 nAChR in vivo. Agonists of the α7 nAChR improve memory and attentional properties and increase immediate early gene expression in the prefrontal cortex and the nucleus accumbens. We show that acute systemic administration of the α7 nAChR agonist SSR180711 (10 mg/kg) result in a significant increase in Fos protein levels in the shell of nucleus accumbens in wild-type mice, but has no effect in the transgene mice. There were fewer cell bodies expressing Fos in the prefrontal cortex of transgene mice, and in this region no induction was achieved after administration with SSR180711 in either of the two groups. These results suggest that overexpression of human Aβ peptides perhaps via direct interaction with α7 nAChR, inhibit α7 nAChR-dependent neurotransmission in vivo and emphasize that clinical trials testing α7 nAChR agonists should be related to the content of Aβ peptides in the patient''s nervous system. [Copyright &y& Elsevier]

Abstract: Nicotinic α7 acetylcholine receptors (α7 nAChR) have been shown to enhance attentional function and aspects of memory function in experimental models and in man. The protein Arc encoded by the effector immediate early gene arc or arg3.1 has been shown to be strongly implicated in long-term memory function. We have sought to determine if α7 nAChR mediate the stimulation of arc gene expression, and if so, where in the brain such activation may occur using semi-quantitative in situ hybridisation. Administration of the novel and selective α7 nAChR agonist, SSR180711 (1, 3 and 10mg/kg) to adolescent rats, produced a dose- and time-dependent increase in the expression of Arc mRNA in the prefrontal cortex and the ventral orbital cortex. By contrast, no change in mRNA levels was detected in the parietal cortex and the CA1 of the hippocampus. These data show that α7 nAChR activates a subset of neurons in the rat prefrontal cortex and this activation likely is important for the attentional effects of this new class of drugs. [Copyright &y& Elsevier]