Comparative analysis of antiproliferative and vasodilator effects of drugs for pulmonary hypertension: Extensive in vitro study in rats and human

Vascul Pharmacol. 2024 Jun:155:107371. doi: 10.1016/j.vph.2024.107371. Epub 2024 Apr 8.

Abstract

An effective pulmonary hypertension (PH) treatment should combine antiproliferative and vasodilator effects. We characterized a wide-range of drugs comparing their anti-proliferative vs vasodilator effects in human and rat pulmonary artery smooth muscle cells (PASMC). Key findings: 1) Approved PH drugs (PDE5 inhibitors, sGC stimulators and PGI2 agonists) are preferential vasodilators. 2) cGMP stimulators were more effective in cells derived from hypertensive rats. 3) Nifedipine acted equally as vasodilator and antiproliferative. 4) quercetin and imatinib were potent dual vasodilator/antiproliferative drugs. 5) Tacrolimus and levosimendan lacked antiproliferative effects. 6) Forskolin, pinacidil and hydroxyfasudil were more effective as antiproliferative in human cells.

Keywords: Proliferation; Pulmonary hypertension; Vascular smooth muscle; Vasodilation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Humans
  • Hypertension, Pulmonary* / drug therapy
  • Hypertension, Pulmonary* / pathology
  • Hypertension, Pulmonary* / physiopathology
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Muscle, Smooth, Vascular / physiopathology
  • Myocytes, Smooth Muscle* / drug effects
  • Myocytes, Smooth Muscle* / metabolism
  • Myocytes, Smooth Muscle* / pathology
  • Pulmonary Artery* / drug effects
  • Pulmonary Artery* / metabolism
  • Pulmonary Artery* / physiopathology
  • Rats
  • Vasodilation / drug effects
  • Vasodilator Agents* / pharmacology

Substances

  • Vasodilator Agents
  • Antihypertensive Agents