Monocrotaline is an 11-membered macrocyclic pyrrolizidine alkaloid derived from the seeds of the Crotalaria spectabilis plant. Monocrotaline is activated to the reactive pyrrole metabolite dehydromonocrotaline in the liver, a reaction that is highly dependent on cytochrome P-450 (CYP3A4). Monocrotaline induces a syndrome characterized, among other manifestations, by pulmonary hypertension, pulmonary mononuclear vasculitis (acute necrotizing pulmonary arteritis in about one-third of the animals), and right ventricular hypertrophy. Monocrotaline is widely used to model pulmonary arterial hypertension in rodents. Monocrotaline aggregates on and activates the extracellular calcium-sensing receptor (CaSR) of pulmonary artery endothelial cells to trigger endothelial damage and, ultimately, induces pulmonary hypertension.