Sex Differences in Sympathetic Neurotransmission in Normotensive Rat Mesenteric Arteries

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Hypertension is less common in premenopausal women than in men possibly due to high estrogen levels in females. The diameter of mesenteric arteries (MA) is an important determinant of system blood pressure and sympathetic nerve activity is a major determinant of MA diameter. Sympathetic nerve supplying MA uses norepinephrine (NE) and ATP as vasoconstrictor transmitters in male rats. We tested the hypothesis that noradrenergic/purinergic neuroeffector transmission to MA also occurs in female rats. Young (10–14 week), normotensive Sprague Dawley male and female rats were used. The estrus cycle stage in female was determined cytologically by vaginal lavage before euthanasia. MA (200 – 250 μm inner diameter) were harvested in a physiological buffer solution and mounted in a pressure (60 mmHg) myograph and inner diameter was measured continuously. Electrical field stimulation (30 stimuli at 0.2–30Hz) and drug addition to the chamber were used to constrict MA. Neurogenic constriction was greater in male compared to female arteries. Neurogenic constriction did not vary with the estrus cycle in female rats. Neurogenic constrictions were blocked by combined application of prazosin (0.1 μM, α1‐adrenergic receptor antagonist) and PPADS (10 μM, P2X‐purinergic receptor antagonist) as well as suramin (100 μM, P2X and P2Y‐purinergic receptor antagonist) in arteries from male and female rats. PPADS/Suramin inhibited ATP and α,β‐methylene ATP, but not KCl, ‐induced MA contraction. Constrictions caused by exogenous NE, ATP,α,β‐methylene ATP or elevated KCl were similar in MA from male and female rats. Immunostaining for tyrosine hydroxylase (a sympathetic nerve marker) revealed no observable differences in nerve density and distribution in MA from male and female rats. Our data indicate that there are fundamental differences in the mechanisms of neurogenic vasoconstriction in MA of male and female rats. Differences in neurotransmission and/or nerve fiber distribution in male and in female rats might contribute to and explain the sex differences in hypertension prevalence between human males and females.Support or Funding InformationSupported by NHLBI 2P01HL07687