SUMMARYMany polygynous, capital breeders exhibit sexual dimorphism with respect to body size and composition. Sexual dimorphism is often facilitated by sex differences in foraging behavior, growth rates and patterns of nutrient deposition during development. In species that undergo extended fasts during development, metabolic strategies for fuel use have the potential to influence future reproductive success by directly impacting somatic growth and acquisition of traits required for successful breeding. We investigated sexual dimorphism associated with metabolic strategies for fasting in developing northern elephant seals. Thirty-one juvenile seals of both sexes were sampled over extended fasts during annual autumn haul-outs. Field metabolic rate (FMR) and the contribution of protein catabolism to energy expenditure were estimated from changes in mass and body composition over 23±5days of fasting (mean ± s.d.). Protein catabolism was assessed directly in a subset of animals based on urea flux at the beginning and end of the fast. Regulatory hormones and blood metabolites measured included growth hormone, cortisol, thyroxine, triiodothyronine, insulin, glucagon, testosterone, estradiol, glucose, urea and -hydroxybutyrate. Males exhibited higher rates of energy expenditure during the fast but spared body protein stores more effectively than females. Rates of protein catabolism and energy expenditure were significantly impacted by hormone levels, which varied between the sexes. These data suggest that sex differences in fuel metabolism and energy expenditure during fasting arise early in juvenile development and may play an important role in the development of adult traits associated with reproductive success.

No abstract

Ageing and the development/progression of hypertension are associated with increased MMP-2 activity in the aorta, which is consistent with ongoing remodelling of the vasculature. However, the underlying mechanisms regulating MMP-2 abundance in ageing and hypertension appear to be divergent, as MT-1 MMP expression is differentially altered. Dual ETA/ETB receptor antagonism did not alter the age-dependent increase in aortic MMP activity in normotensive rats. However, bosentan decreased pro and active MMP-2 activity in senescent SHR rats, indicating that ET modulates late events in vascular remodelling in hypertension.

Despite extensive research and novel treatments, chronic heart failure (CHF) remains a cause of high morbidity and mortality. Mounting evidence suggested that immune activation and inflammation play critical roles in the pathogenesis of CHF. In this review, we examine the current evidence regarding this contemporary pathophysiological mechanism, and evaluate the effects of conventional and novel cardiovascular drugs, such as calcium sensitisers and statins, on the immune and inflammatory mediator's network. Although therapies, which specifically antagonise tumour necrosis factor-alpha have not demonstrated considerable benefit in patients with CHF, there is an increasing evidence to suggest greater value from non-specific anti-inflammatory approaches, including: pentoxifylline, intravenous immunoglobulin, immune modulation therapy, growth hormones, physical training and nutrition regulation. Several innovative therapeutic targets, such as peroxisome proliferator-activated receptor gamma activators, Rho-kinase, p38 mitogen-activated protein kinase, nuclear transcription factor NF-kappaB, recovering or augmenting parasympathetic tone, cardiac resynchronisation therapy, macrophage inhibitors and chemokine receptor antagonists, are briefly discussed in this review. While we have recently demonstrated the potential merits of combining low-dose methotrexate with conventional therapy, through extensively modulating the activated immune and inflammatory mediator's network, there is a need for further rigorous research of this complex network, especially involving current promising therapies which modulate this system. Such evidence has the potential to revolutionise changes for the management of this disorder. Based on the 'heterogeneity' of immune activation and inflammation among different CHF populations, an 'optimised combination treatment' may offer exciting benefits for individual therapy in the future.

Severity of left ventricular hypertrophy (LVH) correlates with elevated plasma levels of neuropeptide Y (NPY) in hypertension. NPY elicits positive and negative contractile effects in cardiomyocytes through Y 1 and Y 2 receptors, respectively. This study tested the hypothesis that NPY receptor-mediated contraction is altered during progression of LVH. Ventricular cardiomyocytes were isolated from spontaneously hypertensive rats (SHRs) pre-LVH (12 weeks), during development (16 weeks Mammalian myocardium contains large quantities of neuropeptide Y (NPY) (Onuoha et al., 1999), mainly colocalized with noradrenaline in perivascular sympathetic neurons innervating cardiac tissue (Franco-Cereceda et al., 1985;Allen et al., 1986). NPY has been implicated in left ventricular hypertrophy (LVH), an initial compensatory response of the heart to pressure overload precipitated by hypertension (Agabiti-Rosei and Muiesan, 2001) because increased plasma levels of the peptide are found in hypertension, myocardial infarction, and heart failure (Maisel et al., 1989) and correlate with severity of LVH (Hulting et al., 1990).NPY can both decrease and increase the contractile response of electrically stimulated rat ventricular cardiomyocytes (Piper et al., 1989;Millar et al., 1991). The negative effect, observed in isoproterenol-treated cells, is due primarily to stimulation of the transient outward current (I to ) and mediated through an inhibitory G protein/adenylate cyclase pathway (Kassis et al., 1987;Piper et al., 1989;Millar et al., 1991). Use of the selective Y 2 receptor agonists, PYY 3-36 and NPY , inferred Y 2 receptor involvement (McDermott et al., 1997), but the finding that long C-terminal fragments of both PYY and NPY also exhibit high affinity for the Y 5 receptor subtype (Hu et al., 1996) emphasizes the need for clarification of receptor subtypes involved in NPY-stimulated cardiomyocyte contraction. NPY alone does not influence the basal level of contraction of cardiomyocytes, but in the presence of 4-aminopyridine, which selectively inhibits I to in these cells, a positive response to NPY is unmasked (Millar et al., 1991). This has been observed also in chicken cardiomyocytes in the absence of rectifier current blockade (Jacques et This work was supported by the British Heart Foundation. Article, publication date, and citation information can be found at