Testosterone is a dilator of resistance arteries in men with congestive heart failure
CJ Malkin1,2, PJ Pugh1, RD Jones2, TH Jones2 & KS Channer1
Heart failure is a syndrome of vaso-constriction and hormone abnormalities. There is an excess of catabolic and vasoconstrictor hormones and a relative deficiency of anabolic hormones. Vaso-dilating drugs improve symptoms in heart failure and inhibition of some catabolic / vasoconstrictor hormones improves prognosis. We aimed to study the direct vascular effects of testosterone resistance arteries from men with heart failure.
6 resistance arteries were harvested from gluteal biopsy from 5 patients with congestive heart failure age (65yrs plusminus 2.2). Vessels were dissected free from connective tissue and mounted on a wire myograph. The vessels were stretched to mimic mean arterial blood pressure (100.3millimetres Hg plusminus 2) and internal diameter calculated at this pressure (418umicrometres plusminus 32.3 ). Tissue viability was confirmed with a test dose of KCL with a minimal acceptable constriction of 1milliNewton. Vessels were then washed with physiological saline and maximally pre-constricted with increasing concentrations of KCL. Testosterone or ethanol (vehicle control) were then added in random order in increasing concentrations and the percentage relaxation from baseline recorded as mean plusminus s.e.m. Variables from the testosterone and ethanol curves were compared with Mann-Whitney U test for non-parametric variables.
Results. The vessels had a maximum contraction of ( 3.9milliNewtons plusminus 1.4 ) to cumulative additions of KCL. The ethanol vehicle had no significant effect on the vessel. Testosterone in concentrations 1x103 Molar and 3x103 Molar caused a rapid and acute relaxation of pre-constricted resistance vessels (-50.4 plusminus 16.8 percentage change: p= 0.002) (-75 plusminus 16.7 percentage change: p=0.002) respectively.
Testosterone in modestly supra-physiological doses is a vasodilator of human resistance arteries in patients with heart failure. Whether this property is clinically relevant to the symptoms of heart failure is unknown but should be the subject of further studies.