The effects of kisspeptin-54 on blood pressure in humans and plasma kisspeptin concentrations in hypertensive diseases of pregnancy

center dot Kisspeptin potently stimulates gonadotrophin release in humans and therefore represents a potential therapy for disorders of reproduction. However, ex vivo studies on human tissue suggest that kisspeptin has vasoconstrictive effects. Thus it is important to determine the effects of kisspeptin on blood pressure and heart rate in humans. Furthermore, plasma kisspeptin concentrations increase markedly in pregnancy but it is currently not known if concentrations are altered in hypertensive diseases of pregnancy. WHAT THIS STUDY ADDS center dot This study demonstrates that states of elevated kisspeptin are not associated with changes in blood pressure or heart rate in humans. Neither are hypertensive diseases of pregnancy associated with altered circulating kisspeptin. This has implications for the future use of kisspeptin as a therapy. AIMS To investigate (i) if kisspeptin administration alters heart rate (HR) or blood pressure (BP) in healthy male and female volunteers, (ii) whether circulating plasma kisspeptin concentrations in healthy pregnant women and women with hypertensive diseases of pregnancy correlate with BP and (iii) whether women with hypertensive diseases of pregnancy have altered plasma kisspeptin concentrations. METHODS We have previously reported the effects of administration of kisspeptin-54 on gonadotrophin secretion in healthy male and female volunteers. In these studies, cardiovascular parameters were not a primary endpoint. However, data were also collected on BP and HR for 4 h post administration of kisspeptin-54. Blood samples were taken from 105 women in the third trimester of pregnancy (27 women with hypertensive diseases of pregnancy and 78 controls). Samples were assayed for plasma kisspeptin immunoreactivity (IR). RESULTS Administration of kisspeptin was not associated with significant changes in HR or BP in healthy men or women. There was no significant correlation between plasma kisspeptin concentration and BP in healthy pregnant women or in those with hypertensive diseases of pregnancy. No significant differences in plasma kisspeptin-IR concentrations were observed between women with hypertensive diseases of pregnancy and normotensive pregnant controls, plasma kisspeptin concentrations +/- SE: controls 2878 +/- 157 pmol l-1; pregnancy-induced hypertension 2696 +/- 299 pmol l-1 (95% CI vs. controls -514, 878 pmol l-1); pre-eclampsia 3519 +/- 357 (95% CI vs. controls -1644, 362 pmol l-1). CONCLUSIONS Elevation of plasma kisspeptin-IR is not associated with an alteration in BP in humans.