Nailfold capillary microscopical and hormonal investigations were carried out in 25 patients with cirrhosis of the liver and in 20 age- and sex-matched controls. Several structural and functional capillary microscopical parameters were significantly different between the group of cirrhotics as a whole and the controls; no capillaroscopic feature helped to distinguish cirrhotics with spiders from those without. Serum estradiol and total testosterone were comparable in cirrhotics and controls; free serum testosterone was reduced in male cirrhotics, particularly in cirrhotics with spider nevi. The estradiol/free testosterone ratio was highest in male cirrhotics with spiders. Cirrhosis, thus, leads to both structural and functional effects on the cutaneous capillary system whether or not spider nevi are present. The presence of spider nevi is accompanied by an increased serum estradiol/free testosterone ratio in male cirrhotics. It remains to be determined whether the hormonal alterations described do indeed play a role in spider nevi formation.
Although endogenous opioids are thought to be involved in the regulation of vasopressin secretion, their precise role is unclear. We studied the effect of the potent nonselective opioid antagonist diprenorphine on the vasopressin response to osmotic (hypertonic saline, ip), hypovolemic (polyethylene glycol, ip), and hypotensive (sodium nitroprusside, sc) stimuli in male rats. We found that diprenorphine sc produced a time- and dose-dependent inhibition of the plasma vasopressin response to the hypovolemic stimulus. This inhibition was greatest 30 min after injection of the drug, but lasted for at least 4 h, was evident at doses as low as 0.0022 mumol/kg, and reached a maximum of about 85% of the stimulated control at a dose of 2.2 mumol/kg. Diprenorphine also inhibited the vasopressin response to an osmotic or a hypotensive stimulus, but the effect was less complete (approximately 50%), required 100-fold higher doses of the drug, and appeared to be bimodal. The potent kappa 1-selective opioid agonist U-50,488H also suppressed the vasopressin response to these stimuli, but the effect was not selective for hypovolemia, and the doses required (0.135-13.5 mumol/kg) were about 10- to 100-fold higher than those of diprenorphine. We postulate, therefore, that diprenorphine potently and preferentially inhibits the vasopressin response to an acute hypovolemic stimulus by antagonizing the effect of some endogenous opioidergic system critical in the volume control system.
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