Relaxin in Systemic Vascular Mechanisms and Function

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DESCRIPTION (provided by applicant): Vascular stiffness is gaining more importance as an independent cardiovascular risk factor especially, in cardiovascular pathologies such as those associated with accelerated aging and chronic hypertension. Although traditionally associated with female reproductive processes, relaxin (Rlx) is emerging as an important modulator of cardiovascular function. When administered to non-pregnant female and male rats, Rlx decreases systemic vascular resistance, and increases cardiac output and global arterial compliance, as well as the compliance of small renal arteries ex vivo. Preliminary studies have shown relaxin mRNA and protein expression in isolated arteries from rats (both male and female) and relaxin and relaxin receptor mRNA expression in cultured human vascular cells. Other preliminary studies have shown that small renal arteries isolated from relaxin deficient mice are characterized by reduced compliance, and increased myogenic reactivity. Therefore, this project proposes to test whether Rlx, irrespective of gender, is also a vascular-derived, locally acting compliance and relaxing factor. We hypothesize that the steady and pulsatile arterial loads are increased, and isolated blood vessels are less compliant and characterized by higher levels of collagen in relaxin deficient mice. Steady and pulsatile arterial loads will be determined using aortic pressure flow measurements in conscious mice. Passive mechanics of isolated arteries from wild type and knockout mice will be assessed using an isobaric pressure arteriograph. Biochemical analyses will be performed to quantify vascular collagen characteristics (e.g., amount, polypeptide chains, crosslinks). Results of this project could identify possible therapeutic applications of relaxin in treating or preventing certain cardiovascular pathologies wherein increased vascular stiffness and vasoconstriction are known to occur.