Upregulation of adrenomedullin and its receptor components during cardiomyocyte hypertrophy induced by chronic inhibition of nitric oxide synthesis in rats

Adrenomedullin may provide a compensatory mechanism to attenuate left ventricular hypertrophy (LVH). Nitric oxide synthase inhibition, induced by chronic administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats, induces cardiac hypertrophy in some, but not all cases; there are few reports of direct assessment of cardiomyocyte parameters. The objective was to characterize hypertrophic parameters in left (LV) and right ventricular (RV) cardiomyocytes after administration of L-NAME to rats for 8 wk and to determine whether adrenomedullin and its receptor components were upregulated. After treatment with L-NAME (20 and 50 mg x kg(-1) x day(-1)), compared with nontreated animals, 1) systolic blood pressure increased (by 34.2 and 104.9 mmHg), 2) heart weight-to-body wt ratio increased 24.1% at the higher dose (P

Myocardial expression of the endothelin system in endotoxin-treated rats.

Although circulating plasma levels of endothelin (ET)-1 are elevated in endotoxemia, little is known about the myocardial expression of the ET system in endotoxic shock. We assessed the temporal mRNA expression pattern of key components of the ET system (pre-pro ET (ppET) -1, -2, ET-converting enzyme-1, ETA and ETB receptors) by reverse transcription polymerase chain reaction in a rat model of early endotoxic shock. Lipopolysaccharide (5 mg/kg, i.p.) caused a transient increase (p 12-fold increase; p

The energy costs of sexual dimorphism in mole-rats are morphological not behavioural.

Different reproductive strategies of males and females may lead to the evolution of differences in their energetic costs of reproduction, overall energetic requirements and physiological performances. Sexual dimorphism is often associated with costly behaviours (e.g. large males might have a competitive advantage in fighting, which is energetically expensive). However, few studies of mammals have directly compared the energy costs of reproductive activities between sexes. We compared the daily energy expenditure (DEE) and resting metabolic rate (RMR) of males and females of two species of mole-rat, Bathyergus janetta and Georychus capensis (the former is sexually dimorphic in body size and the latter is not) during a period of intense digging when males seek females. We hypothesized that large body size might be indicative of greater digging or fighting capabilities, and hence greater mass-independent DEE values in males of the sexually dimorphic species. In contrast to this prediction, although absolute values of DEE were greater in B. janetta males, mass-independent values were not. No differences were apparent between sexes in G. capensis. By comparison, although RMR values were greater in B. janetta than G. capensis, no differences were apparent between the sexes for either species. The energy cost of dimorphism is most likely to be the cost of maintenance of a large body size, and not the cost of behaviours performed when an individual is large.

Effect of angiotensin-related antihypertensives on brain neurotransmitter levels in rats.

The extensive clinical experience of angiotensin converting enzyme inhibitors and angiotensin AT(1) receptor antagonists as antihypertensive agents provide numerous examples of anecdotal evidence of improvements in cognition and mood. This study aimed to determine the effect of chronic treatment with the angiotensin converting enzyme inhibitor, perindopril, and the angiotensin AT(1) receptor antagonist, candesartan, on central neurotransmitter levels in the rat. Perindopril (1.0mg/kg/day) or candesartan (10mg/kg/day) was administered via the drinking water at for 1 week, while controls received water alone. At the end of treatment rats were sacrificed, brains removed and discrete regions dissected and analysed for noradrenaline, dopamine and its major metabolites, and serotonin content. As shown previously we found an increase in striatal dopamine levels after perindopril treatment, though this did not extend to the mesolimbic system with neurotransmitter levels unchanged in the hippocampus, nucleus accumbens and frontal cortex. Conversely, candesartan administration produced no change in dopamine, but significant decreases in both DOPAC and HVA in the striatum. In addition chronic candesartan infusion produced a significant increase in the levels of hippocampal noradrenaline and serotonin; and frontal cortex serotonin content. These results demonstrate that while angiotensin converting enzyme inhibitors and angiotensin AT(1) receptor antagonists act as antihypertensives by affecting the renin-angiotensin system, they have divergent actions on brain neurochemistry.

Mole-rats from higher altitudes have greater thermoregulatory capabilities

Subterranean mammals (those that live and forage underground) inhabit a challenging microenvironment, with high levels of carbon dioxide and low levels of oxygen. Consequently, they have evolved specialised morphological and physiological adaptations. For small mammals that inhabit high altitudes, the effects of cold are compounded by low oxygen partial pressures. Hence, subterranean mammals living at high altitudes are faced with a uniquely demanding physiological environment, which presumably necessitates additional physiological adjustments. We examined the thermoregulatory capabilities of two populations of Lesotho mole-rat Cryptomys hottentotus mahali that inhabit a 'low' (1600 in) and a 'high' (3200 m) altitude. Mole-rats from the high altitude had a lower temperature of the lower critical point, a broader thermoneutral zone, a lower thermal conductance and greater regulatory non-shivering thermogenesis than animals from the lower altitude. However, minimum resting metabolic rate values were not significantly different between the populations and were low compared with allometric predictions. We suggest that thermoregulatory costs may in part be met by animals maintaining a low resting metabolic rate. High-altitude animals may adjust to their cooler, more oxygen-deficient environment by having an increased non-shivering thermogenesis whilst maintaining low thermal conductance. (c) 2006 Elsevier Inc. All rights reserved.

Efficient heterogeneous asymmetric catalysis of the Mukaiyama aldol reaction by silica- and ionic liquid-supported Lewis acid copper(II) complexes of bis(oxazolines)

Lewis acid complexes based on copper(II) and an imidazolium-tagged bis(oxazoline) have been used to catalyse the asymmetric Mukaiyama aldol reaction between methyl pyruvate and 1-methoxy-1-tri-methylsilyloxypropene under homogeneous and heterogeneous conditions. Although the ees obtained in ionic liquid were similar to those found in dichloromethane, there was a significant rate enhancement in the ionic liquid with reactions typically reaching completion within 2 min compared with only 55% conversion after 60 min in dichloromethane. However, this rate enhancement was offset by lower chemoselectivity in ionic liquids due to the formation of 3-hydroxy-1,3-diphenylbutan-1-one as a by-product. Supporting the catalyst on silica or an imidazolium-modified silica using the ionic liquid or in an ionic liquid-diethyl ether system completely suppressed the formation of this by-product without reducing the enantioselectivity. Although the heterogeneous systems were characterised by a drop in catalytic activity the system could be recycled up to five times without any loss in conversion or ee.

Lewis acid platinum complexes of conformationally flexible NUPHOS diphosphines: Highly efficient catalysts for the carbonyl-ene reaction

Enantiopure Lewis acid complexes of conformationally flexible acyclic and monocyclic NUPHOS diphosphines, delta- and lambda-[(NUPHOS)Pt(OTf)(2)], are efficient catalysts for the carbonyl-ene reaction between various unsymmetrical 1,1'-disubstituted alkenes and phenylglyoxal or ethyl glyoxylate. While catalyst performance was substrate dependent, ee values as high as 95% and yields up to 90% have been obtained. In a number of cases catalysts generated from delta- and lambda-[(NUPHOS)Pt{(S)-BINOL}] showed marked enhancements in enantioselectivity in ionic liquids compared with organic media. Although an enhancement in enantioselectivity was not obtained for all substrate combinations in such cases, the enantioselectivities were comparable to those obtained in dichloromethane. Furthermore, although the ee's are initially comparable in both the ionic liquid and dichloromethane, a gradual erosion of ee with time was found in the organic solvent, whereas the ee remained constant in the ionic liquid. Preliminary kinetic investigations suggest that the decrease in ee may be due to a faster racemization of the catalyst in dichloromethane compared with the ionic liquid.

Highly efficient asymmetric hetero-Diels-Alder reactions of carbonyl compounds catalyzed by Lewis acid platinum complexes of conformationally flexible NUPHOS-type diphosphines

Conformationally flexible NUPHOS-type diphosphines have been resolved as their diastereopure platinum BINOLate complexes delta- and lambda-[(NUPHOS)Pt{(S)-BINOL}] and the corresponding enantiopure Lewis acids delta- and lambda-[(NUPHOS)Pt(OTf)(2)], being generated by protonation with trifluoromethanesulfonic acid, act as highly efficient catalysts for the hetero-Diels-Alder reaction of nonactivated conjugated dienes with aryl glyoxals and glyoxylate esters, giving ee's as high as 99%.