Relaxin modifies systemic arterial resistance and compliance in conscious, nonpregnant rats.
Relaxin emanates from the corpus luteum of the ovary and circulates during pregnancy. Because the hormone is a potent renal vasodilator and mediates the renal vasodilation and hyperfiltration of pregnancy in conscious rats, we reasoned that it might also contribute to the broader cardiovascular changes of pregnancy. We began investigating this concept by testing whether relaxin can modify systemic arterial hemodynamics and load when chronically administered to nonpregnant rats. The major objectives of the present work were to determine whether relaxin administration to nonpregnant rats 1) modifies cardiac output (CO), systemic vascular resistance, and global arterial compliance (AC), and 2) regulates the passive mechanics of isolated arteries. To accomplish the first objective, we developed a conscious rat model for assessment of global AC. Passive mechanics of small renal arteries were assessed using a pressure arteriograph. Chronic administration of recombinant human relaxin by sc osmotic minipump to conscious, female, nonpregnant rats reduced the steady arterial load by decreasing systemic vascular resistance, increased CO, and reduced the pulsatile arterial load by increasing global AC as quantified by two indices-AC estimated from the diastolic decay of aortic pressure and CO and AC estimated by the ratio of stroke volume-to-pulse pressure. In another group of rats, relaxin administration also regulated the passive mechanics of small renal arteries, indicating that, in addition to reduction in vascular smooth muscle tone, modification of the vascular structure (e.g. extracellular matrix) contributes to the increase in global AC. These findings suggest a role for relaxin in the systemic hemodynamic changes of pregnancy, as well as novel therapeutic potential for relaxin in modifying arterial stiffness and cardiac afterload.
Conrad
Kirk P
KP
Department of Obstetrics and Gynecology and Reproductive Sciences,University of Pittsburgh School of Medicine, and Magee-Women's Research Institute, University of Pittsburgh, Pennsylvania 15213, USA. rsikpc@mwri.magee.edu.
Debrah
Dan O
DO
Novak
Jackie
J
Danielson
Lee A
LA
Shroff
Sanjeev G
SG
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003187:Compliance / Q000187:drug effects; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D030762:Estrous Cycle; D005260:Female; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D012065:Relaxin / Q000494:pharmacology* / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*
D012065:Relaxin