The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?

Abstract

Conrad KP, Davison JM. The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?. Am J Physiol Renal Physiol 306: F1121-F1135, 2014. First published March 19, 2014 doi:10.1152/ajprenal.00042.2014.-During the first trimester of human pregnancy, the maternal systemic circulation undergoes remarkable vasodilation. The kidneys participate in this vasodilatory response resulting in marked increases in renal plasma flow (RPF) and glomerular filtration rate (GFR). Comparable circulatory adaptations are observed in conscious gravid rats. Administration of the corpus luteal hormone relaxin (RLN) to nonpregnant rats and humans elicits vasodilatory changes like those of pregnancy. Systemic and renal vasodilation are compromised in midterm pregnant rats by neutralization or elimination of circulating RLN and in women conceiving with donor eggs who lack a corpus luteum and circulating RLN. Although RLN exerts both rapid (minutes) and sustained (hours to days) vasodilatory actions through different molecular mechanisms, a final common pathway is endothelial nitric oxide. In preeclampsia (PE), maternal systemic and renal vasoconstriction leads to hypertension and modest reduction in GFR exceeding that of RPF. Elevated level of circulating soluble vascular endothelial growth factor receptor-1 arising from the placenta is implicated in the hypertension and disruption of glomerular fenestrae and barrier function, the former causing reduced K f and the latter proteinuria. Additional pathogenic factors are discussed. Last, potential clinical ramifications include RLN replacement in women conceiving with donor eggs and its therapeutic use in PE. Another goal has been to apply knowledge gained from investigating circulatory adaptations in pregnancy toward identifying and developing novel therapeutic strategies for renal and cardiovascular disease in the nonpregnant population. So far, one candidate to emerge is RLN and its potential therapeutic use in heart failure. renal hemodynamics; glomerular filtration; osmoregulation; relaxin; nitric oxide; assisted reproductive technology; glomerular endotheliosis; soluble vascular endothelial growth factor receptor-1; heart failure Renal Plasma Flow and Glomerular Filtration in Normal PregnancyMARKED VASODILATION OF THE MATERNAL CIRCULATION occurs in the first trimester of human pregnancy. Consequently, there is a precipitous and profound decline in systemic vascular resistance (SVR) that in turn abets a reciprocal increase in cardiac output (CO) of ϳ40% or 2 l/min lasting throughout pregnancy (23,163). Vasodilation of nonreproductive organs like the kidneys accounts mostly for the early gestational fall in SVR and rise in CO. The fall in SVR is nearly offset by the rise in CO; hence, mean arterial pressure (MAP) declines, but only modestly, by 5-10 mmHg (23,38,163). Although counterintuitive, this metamorphosis of the maternal circulation is virtually complete by the end of the first or beginning of the second trimester, when fetal crown rump length and place...

A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus

“…Urinary protein excretion is also slightly increased and only levels 300 mg/24 h are considered pathological [58,59].…”

Pregnancy-associated cardiomyopathies

“…These circulatory changes are thought to condition the maternal system for the rapid growth phase of the foetus and placenta in the 2nd half of pregnancy, when oxygen and nutrient demands are r ising exponentially. These changes need powerful dilatory mechanism(s) to counteract compensatory structural and functional hypertrophy for which the pregnancy hormone relaxin (RLN) may be responsible [4].…”

“…Pre-eclampsia has been defined as onset of sustained hypertension (>140 mm Hg systolic or >90 mm Hg diastolic blood pressure) with development of proteinuria of at least 1+ on dipstick or >300 mg per 24 hours after 20 weeks of gestation. Severe disease is defined as blood pressure >160 mm Hg systolic or >110 mm Hg diastolic, proteinuria >5 g per 24 hours, neurological symptoms such as seizures, pulmonary oedema, hepatic or renal dysfunction, thrombocytopenia or fetal growth restriction [4]. Pre-eclampsia is a leading cause for premature delivery with high risk for maternal, fetal and neonatal morbidity and mortality [4].…”

“…Severe disease is defined as blood pressure >160 mm Hg systolic or >110 mm Hg diastolic, proteinuria >5 g per 24 hours, neurological symptoms such as seizures, pulmonary oedema, hepatic or renal dysfunction, thrombocytopenia or fetal growth restriction [4]. Pre-eclampsia is a leading cause for premature delivery with high risk for maternal, fetal and neonatal morbidity and mortality [4]. To date, no specific therapies for pre-eclampsia are available and pharmacological control of blood pres-REVIEW ARTICLE generation sequencing may be helpful in these patients to identify disease-causing factors and co-factors.…”

Preliminary in vitro analysis of mechanism of cardiac microvascular endothelial barrier function

“…Endothelial cells (ECs) function as a semipermeable barrier between blood and interstitial tissues, thereby having antithrombotic and regulatory effects on endocrine function and angiostasis. EC injury can cause endothelial dysfunction, which is closely associated with the onset and progression of heart failure (Conrad and Davison, 2014;Masterson et al, 2015). EC damage can be caused by many factors such as cytokines, reactive oxygen species, and lipase.…”