Periodic injections of Relaxin 2, its pharmacokinetics and remodeling of rat hearts

Biochem Pharmacol. 2024 Mar 15:116136. doi: 10.1016/j.bcp.2024.116136. Online ahead of print.ABSTRACTRelaxin-2 (RLX), a critical hormone in pregnancy, has been investigated as a therapy for heart failure. In most studies, the peptide was delivered continuously, subcutaneously for 2 weeks in animals or intravenously for 2-days in human subjects, for stable circulating [RLX]. However, pulsatile hormone levels may better uncover the normal physiology. This premise was tested by subcutaneously injecting Sprague Dawley rats (250 g, N = 2 males, 2 females/group) with human RLX (0, 30, 100, or 500 µg/kg), every 12 h for 1 day, then measuring changes in Nav1.5, connexin43, and β-catenin, 24 h later. Pulsatile RLX was measured by taking serial blood draws, post-injection. After an injection, RLX reached a peak in ∼ 60 min, fell to 50 % in 5-6 h; injections of 0, 30, 100 or 500 µg/kg yielded peak levels of 0, 11.26 ± 3.52, 58.33 ± 16.10, and 209.42 ± 29.04 ng/ml and residual levels after 24-hrs of 0, 4.9, 45.1 and 156 pg/ml, respectively. The 30 µg/kg injections had no effect and 100 µg/kg injections increased Nav1.5 (25 %), Cx43 (30 %) and β-catenin (90 %). The 500 µg/kg injections also increased Nav1.5 and Cx43 but were less effective at upregulating β-catenin (up by 25 % vs. 90 %). Periodic injections of 100 µg/kg were highly effective at increasing the expression of Nav1.5 and Cx43 which are key determinants of conduction velocity in the heart and the suppression of a...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research