Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats.

UNLABELLED: Obesity is related to insulin resistance and hypertension, but the underlying mechanisms are unclear. Insulin exerts both vasodilator and vasoconstrictor effects on muscle resistance arteries, which may be differentially impaired in obesity. OBJECTIVES: To investigate whether vasodilator and vasoconstrictor effects of insulin are impaired in muscle resistance arteries of obese rats and the roles of Akt and endothelial NO synthase (eNOS). METHODS/RESULTS: Effects of insulin were studied in resistance arteries isolated from cremaster muscles of lean and obese Zucker rats. In arteries of lean rats, insulin increased activity of both NO and endothelin (ET-1), resulting in a neutral effect under basal conditions. In arteries of obese rats, insulin induced endothelin-mediated vasoconstriction (-15 +/- 5% at 1 nM, P < 0.05 vs. lean). Insulin induced vasodilatation during endothelin receptor blockade in arteries of lean rats (20 +/- 5% at 1 nM) but not in those of obese rats. Inhibition of NO synthesis increased vascular tone (by 12 +/- 2%) and shifted insulin-mediated vasoreactivity to vasoconstriction (-25 +/- 1% at 1 nM) in lean rats but had no effect in arteries of obese rats, indicating reduced NO activity. Protein analysis of resistance arteries revealed that insulin-mediated activation of Akt was preserved in obese rats, whereas expression of eNOS was markedly decreased. CONCLUSIONS: Vasodilator but not vasoconstrictor effects of insulin are impaired in muscle resistance arteries of obese rats, and this selective impairment is associated with decreased protein levels of eNOS. These findings provide a new mechanism linking obesity to insulin resistance and hypertension.

Renal microvascular constriction to membrane depolarization and other stimuli: pivotal role for rho-kinase.

Contraction of vascular smooth muscle is determined not only by levels of intracellular free calcium but also by the sensitivity of its contractile apparatus. A potential modulator of the latter is rho-kinase. We addressed the question of a possible central role for rho-kinase in the regulation of periglomerular microvascular tone. In the rat hydronephrotic kidney model, diameter changes of distal interlobular arteries, afferent and efferent arterioles were measured using three distinctly different stimuli: intravascular pressure changes, angiotensin II (AngII) and membrane depolarization, which is a physiological component of many signaling pathways, as evoked in two ways. Two selective, structurally different rho-kinase inhibitors, Y-27632 and HA-1077, were employed, as well as a selective protein kinase C alpha inhibitor. Preglomerular vasoconstriction induced by direct membrane depolarization, increases in pressure or AngII all depended for their effect on rho-kinase. A differing role for rho-kinase in efferent arteriolar constriction to AngII as compared to preglomerular microvessels was not found. In conclusion, our data indicate that in the kidney, rho-kinase is involved in a variety of signaling pathways leading to microvascular constriction. It plays a pivotal role not only in preglomerular but also in postglomerular tone.

Gender-specific effects of social housing in rats after chronic mild stress exposure.

UNLABELLED: Stress plays an important role in the development of affective disorders. Women show a higher prevalence for these disorders than men. The course of a depression is thought to be positively influenced by social support. The authors have used a chronic mild stress model in which rats received footshocks daily for 3 weeks. Since rats are social animals we hypothesized that "social support" might reduce the adverse effects of chronic stress. To test this hypothesis, male and female rats were housed individually or socially in unisex groups of four rats. An open field test was repeated four times during the 3 weeks of treatment. Neuronal activation in the paraventricular nucleus of the hypothalamus (PVN) and dorsal raphe nucleus (DRN) in response to stress was measured the last day with c-fos. Chronic stress exposure increased locomotor activity in the open field, especially during the first minute. This was most pronounced in the individually housed females. In females, social housing prevented the stress-induced increase of locomotor activity, while in males social housing had no effect. Fos immunoreactive (FOS-ir) in the PVN was increased in all stress-exposed groups, except for the socially housed females due to a higher FOS-ir in controls. Individually housed males and socially housed females showed increased FOS-ir in the DRN and the increase was almost significant in socially housed males. IN CONCLUSION: These results show that social housing can enhance coping with stress in female rats, whereas in male rats group housing did not have a positive influence on stress-sensitivity.