title: Relaxin increases cardiac output and reduces systemic arterial load in hypertensive rats.
abstract: Chronic administration of recombinant human relaxin (rhRLX) to conscious, normotensive rats (male and female) increases cardiac output (CO) and global arterial compliance (ACg) and reduces systemic vascular resistance (SVR) with no change in mean arterial pressure (MAP). Effects (magnitude and temporal pattern) of relaxin on systemic hemodynamics and arterial properties in hypertensive animal models are not known. Accordingly, the major goal of the present study was to determine the cardiovascular effects of rhRLX in hypertensive rats using 2 models: Long-Evans rats chronically administered angiotensin II (AII) and spontaneously hypertensive rats (SHR). CO and systemic arterial load, as quantified by SVR and ACg, were obtained using methods reported previously by us. In rats with AII-induced hypertension, acute rhRLX administration (up to 6 hours) significantly increased CO and ACg (24.9+/-3.9 and 34.3+/-12.6% above baseline, respectively) and significantly decreased SVR (17.2+/-3.5%) without changing MAP. In contrast, acute rhRLX administration to SHR and normotensive rats for up to 6 hours failed to produce any significant changes in CO, ACg, SVR, or MAP. However, chronic rhRLX administration (1 to 7 days) to SHR yielded significant changes (24.0+/-8.1 and 22.3+/-6.6% increases in CO and ACg, respectively, and a 13.3+/-5.3% decrease in SVR, with no change in MAP). In conclusion, rhRLX increases CO and reduces arterial load in hypertensive rats without reducing MAP. However, the time course of response to rhRLX treatment is dependent on the model of hypertension such that rats characterized by AII-mediated hypertension responded more rapidly to rhRLX administration than SHR.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, PA, USA.
authors.forename: Dan O
authors.initials: DO
authors.lastname: Debrah
authors.forename: Kirk P
authors.initials: KP
authors.lastname: Conrad
authors.forename: Arundhathi
authors.initials: A
authors.lastname: Jeyabalan
authors.forename: Lee A
authors.initials: LA
authors.lastname: Danielson
authors.forename: Sanjeev G
authors.initials: SG
authors.lastname: Shroff
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001158:Arteries / Q000503:physiopathology*; D002302:Cardiac Output / Q000187:drug effects*; D003187:Compliance / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D007260:Infusion Pumps; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D020318:Rats, Long-Evans; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012065:Relaxin / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents
chemical_list: D011994:Recombinant Proteins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012065:Relaxin