Cardiovascular actions of parathyroid hormone/parathyroid hormone-related protein signaling

All osteotropic hormones have vasculotropic actions. This pithy statement of fact most certainly holds true for the prototypic bone anabolic polypeptides parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) (aka PTHLH). The cardiovascular actions of PTH were first identified in 1925, when Collip and Clark injected anesthetized Dog 164 with intravenous parathyroid extract and documented hypotensive actions. However, only since the end of the 20th century has the fundamental role of PTH/PTHrP receptor (PTH1R) signaling in cardiovascular development, physiology, and disease been fully vetted-but this is not yet widely appreciated. For example, PTH1R signaling is required for normal aortic valve and myocardial development. Paracrine vascular smooth muscle PTHrP/PTH1R signaling has emerged as important in the homeostatic regulation of renovascular blood flow, while endothelial PTH1R actions convey the endocrine regulation of blood flow to bone in response to PTH. In addition to its bone anabolic actions, intermittent pharmacological dosing with PTH(1-34) mitigates the endothelial dysfunction associated with aging and suppresses arteriosclerotic responses to dysmetabolic states such as diabetes. These observations, among others, provide a second “bookend” that, with Collip and Clark’s early observation, serves to brace the first century of PTH/PTHrP research-a century that has continuously pointed to cardiovascular actions of the PTH family of ligands. Thus, a fundamental understanding of PTH/PTHrP biology must encompass a better understanding of actions within and upon the cardiovascular system.