Progesterone enhances adrenergic control of skin blood flow in women with high but not low orthostatic tolerance

Women are more susceptible to orthostatic intolerance. Peripheral α-adrenergic responsiveness is important in orthostasis and is lower in women compared to men, and is modulated by female sex hormones. We tested the hypothesis that oestradiol attenuates peripheral cutaneous adrenergic responses in women with low orthostatic tolerance (LT), whereas progesterone enhances adrenergic responses in women with high orthostatic tolerance (HT). After completing a maximal lower body negative pressure test to determine level of orthostatic tolerance (cumulative stress index, CSI), women self administered a gonadotropin releasing hormone (GnRH) antagonist for 16 days to suppress endogenous sex hormone production. Oestradiol (E2, 0.2 mg day−1, patch; days 4–16), and progesterone (P4, 200 mg day−1, oral; days 12–16) were administered. Skin blood flow responses to graded intradermal microdialysis infusions of noradrenaline (NA) were measured during GnRH antagonist, E2, and E2+P4, in eight HT (s.e.m. = 22 ± 1 years, CSI −871 ± 86 mmHg min) and eight LT (21 ± 1 years, CSI −397 ± 65 mmHg min) women. In separate probes, NA was infused alone, and co-infused with the nitric oxide synthase inhibitor NG-monomethyl-l-arginine (l-NMMA, 10 mm), the non-selective cyclooxygenase inhibitor ketorolac tromethamine (Keto, 10 mm), and combined l-NMMA + Keto (10 mm each). Progesterone administration enhanced adrenergic responses in HT women (logEC50 GnRH −4.02 ± 0.39, E2+P4−5.18 ± 0.31, P < 0.05); this response was reversed with Keto (E2+P4 logEC50 NA+Keto −3.82 ± 0.35, P < 0.05). In contrast, no change in adrenergic responsiveness occurred in LT women during any hormone condition. These data indicate differential regulation of cutaneous adrenergic responses by progesterone via the cyclooxygenase pathway in women with high and low orthostatic tolerance

Free radicals and antioxidants at a glance using EPR spectroscopy

The delicate balance between the advantageous and detrimental effects of free radicals is one of the important aspects of human (patho)physiology. The controlled production of reactive oxygen and nitrogen species has an essential role in the regulation of various signaling switches. On the other hand, imbalanced generation of radicals is highly correlated with the pathogenesis of many diseases which require the application of selected antioxidants to regain the homeostasis. In the era of growing interest for redox processes, electron paramagnetic resonance (EPR) spectroscopy is arguably the best-suited technique for such research due to its ability to provide a unique insight into the world of free radicals and antioxidants. Herein, I present the principles of EPR spectroscopy and the applications of this method in assessing: (i) the oxidative status of biological systems, using endogenous long-lived free radicals (ascorbyl radical (Asc(center dot)), tocopheroxyl radical (TO center dot), melanin) as markers; (ii) the production of short-lived radicals (hydroxyl radical (OH center dot), superoxide radical anion (O-2(-)), sulfur-and carbon-centered radicals), which are implicated in both, oxidative stress and redox signaling; (iii) the metabolism of nitric oxide (NO center dot); (iv) the antioxidative properties of various drugs, compounds, and natural products; (v) other redox-relevant parameter. Besides giving a comprehensive survey of up-to-date literature, I also provide illustrative examples in sufficient detail to provide a means to exploit the potential of EPR in biochemical/physiological/medical research. The emphasis is on the features and characteristics (both positive and negative) relevant for EPR application in clinical sciences. My aim is to encourage fellow colleagues interested in free radicals and antioxidants to expand their base knowledge or methods used in their laboratories with data acquired by EPR or some of the EPR techniques outlined in this review, in order to boost up the exciting area of redox science