Pulmonary hypertension modifies responsiveness of sinoatrial cells of rat hearts to adrenomimetics and activators of ATP-sensitive K+ channels in a gender-dependent way.
The aim of this paper was to find out how pulmonary arterial hypertension (PAH) affects heart rate in male and female rats. Additionally, the concentration of tumor necrosis factor alpha (TNF-alpha) was monitored. Male and female rats were treated by monocrotaline (i.p., 60 mg/kg B.W.) or by equivalent volume of normal saline solution (n=40) and after 4 weeks right auriculae containing sinoatrial cells have been isolated and examined. We have measured heart rate of spontaneously beating right auriculae and serum level of TNF-alpha. In females with PAH, isoprenaline curve was shifted to the left (pD2 increased from 10,9+/-3 to 15+/-3, n=10, P<0,05), but in males with PAH maximal acceleration of beating rate induced by isoprenaline decreased from 175+/-10 to 146+/-8 beats/min, P<0.05). Additionally, reduction in heart rate induced by rilmakalim was more significantly decreased in females (from -89+/-7 to - 49+/-3 beats/min, n=10, p<0.01) than in males (from - 68+/-6 to - 46+/-4 beats/min, P<0.05) with PAH. We did not detect any changes in TNF-alpha in any experimental group. Our results imply that pulmonary hypertension increased sensitivity of sinoatrial cells to isoprenaline and decreased efficacy of rilmakalim to reduce heart rate more significantly in females then in males.
Department of Pharmacology, Medical University of Gdansk, Gdansk, Poland. ikocic@amg.gda.pl
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D012737:Sex Factors; D012849:Sinoatrial Node / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D002839:Chromans; D054086:KATP Channels; D011759:Pyrrolidines; D014409:Tumor Necrosis Factor-alpha; C075012:rilmakalim; D016686:Monocrotaline; D007545:Isoproterenol