title: Acute pulmonary hemodynamic effects of intravenous copper sulfate: role of alpha-adrenergic system.
abstract: We investigated the acute pulmonary hemodynamic effects of intravenous copper sulfate (CuSO4) infusion and its mechanism of action in six groups of conscious sheep (total 40). After 300 mg CuSO4 alone, mean pulmonary artery pressure (Ppa) increased from 10.3 to 22.5 Torr and pulmonary artery wedge pressure (Ppaw) from 3.5 to 7.6 Torr, whereas systemic arterial pressure (Psa) increased from 95 to 102 Torr. Cardiac output (Qp) decreased from 4.7 to 3.3 l/min. Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) increased to 320 and 160% of base line, respectively. The hemodynamic changes correlated well with serum copper, which increased from a base-line value of 0.12 to 3.5 mg/dl after the CuSO4. Serum dopamine beta-hydroxylase increased from 3.2 U/l before CuSO4 injection to 5.7 after its administration, signifying activation of adrenergic nervous system. H1-histamine receptor blockade with chlorpheniramine failed to prevent the effects of CuSO4. Pretreatment with methysergide, a serotonin antagonist, partially attenuated the effects of CuSO4. Phenoxybenzamine, an alpha-adrenergic receptor blocker, and 6-hydroxydopamine, a catecholamine depleting agent, completely blocked the effects of CuSO4. beta-Adrenergic receptor blockade with propranolol enhanced the effects of CuSO4. We conclude, that, in conscious sheep, acute infusion of CuSO4 caused a marked reversible increase in PVR with a slight transient increase in SVR, and this pulmonary hypertension was produced by stimulation of the alpha-adrenergic nervous system.
mesh_terms: D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D003300:Copper / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000506:poisoning*; D019327:Copper Sulfate; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D007275:Injections, Intravenous; D008784:Methysergide / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012756:Sheep; D013431:Sulfates / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000506:poisoning*
chemical_list: D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D013431:Sulfates; D010643:Phenoxybenzamine; D002744:Chlorpheniramine; D003300:Copper; D011433:Propranolol; D019327:Copper Sulfate; D008784:Methysergide