Alterations in vasomotor systems and mechanics of resistance-sized mesenteric arteries from SHR and WKY male rats following in vivo testosterone manipulation

Abstract

BackgroundTestosterone (T) and the sympathetic nervous system each contribute to the pathology of hypertension. Altered blood vessel reactivity is also associated with the pathology of high blood pressure. The purpose of this study was to examine the effects of T manipulation in the regulation of resistance-sized blood vessel reactivity.MethodsAdult spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) male rats at 8 weeks of age were used. The rats were divided into groups consisting of gonadally intact controls (CONT), castrate with sham implant (CAST) and castrate with T implant (CAST + T) (n = 6 to 12 per group). Following a short-term period of T treatment (approximately 4 weeks), plasma norepinephrine (NE) and plasma T were assessed by performing high-performance liquid chromatography and RIA, respectively. Resistance-sized mesenteric artery reactivity was assessed on a pressurized arteriograph for myogenic reactivity (MYO), phenylephrine (PE) responsiveness and passive structural mechanics.ResultsSHR and WKY males exhibited similar physiological trends in T manipulation, with castration significantly lowering plasma T and NE and T replacement significantly increasing plasma T and NE. T manipulation in general resulted in significant alterations in MYO of second-order mesenteric arteries, with T replacement decreasing MYO in SHR (P < 0.05) compared to CONT, T replacement increasing MYO, and CAST decreasing MYO in WKY rats (P < 0.001) compared to CONT rats. Additionally, PE-induced constriction was significantly altered in both strains following T treatment, with the effective concentration of PE to constrict the vessel to 50% of the total diameter significantly increased in the CAST + T SHR compared to CONT (P < 0.05). Comparisons of passive structural mechanics between SHR and WKY treatment groups indicated in SHR a significantly increased wall-to-lumen ratio and decreased circumferential wall stress compared to WKY treatment groups.ConclusionsThese data suggest that T and NE are involved in a complex interaction with both myogenic reactivity and structural alterations of resistance-sized blood vessels and that these factors likely contribute to the development and maintenance of hypertension.

Adolescent sleep patterns in humans and laboratory animals

“…A hallmark of human brain development is a rapid proliferation of synaptic connections in early childhood, followed by a large overall decrease until maturation. This synaptic pruning, along with parallel increases in axon myelination, is believed to increase the efficiency of cortical networks, and is largely credited for many of the cognitive improvements gained during adolescence (Giedd et al, 2012). Feinberg et al (1990) pointed out that the decline in delta power during adolescence closely parallels the time course of synaptic pruning and diminishing cerebral metabolic rate.…”

“…However, perhaps the most convincing evidence comes from a recent study that found a strong correlation between SWA and cortical grey matter volume measured by magnetic resonance imaging during adolescence (Buchmann et al, 2011). It is worth noting that sex differences in the developmental timing of delta power decline (Campbell et al, 2012) mimic sex differences in the decline in grey matter volume during adolescence (Giedd et al, 2012). Interestingly, the adolescent decline in delta power tightly correlates with pubertal development driven by androgens (Campbell et al, 2012), and recent studies link androgen receptor polymorphisms and adolescent cortical pruning (Raznahan et al, 2010), further suggesting a connection between the two phenomena, although it remains unclear whether the relevant androgens are of gonadal or adrenal origin (as theorized by Campbell, 2006, 2011).…”

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“…Each is selectively activated by fatty acid or cholesterol derivatives [11-13]. HNF4α also plays a major role in liver development [13]. A liver–specific deletion of HNF4α in mice enhances hepatic steatosis [14] and substantially affects Cyp expression [15].…”

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“…Overall, men use more drugs and are 2–3 times more likely to have a drug dependence problem than women; whereas, women show earlier initiation of use and greater escalation of drug taking (Becker et al 2012). This is especially true for stimulants like cocaine and nicotine for which women show higher rates of cocaine use, a younger age of onset, and maintain abstinence for a shorter time-period than men (DeVito et al 2014; McCance-Katz et al 1999; Kosten et al 1993; for review, see Fattore et al 2008).…”