Isolated Intrapulmonary Arterial Responses To Vasoactive Amines and Prostaglandins

Abstract

<p>The response of the intrapulmonary artery (IPA) to a variety of endogenous lung amines and prostaglandins (PG) was examined to determine if a differential sensitivity to these vasoactive substances existed between segments taken from two sites on the artery. Longitudinal strips of proximal (PIPA) and distal (DIPA) segments of the left lower lobar intrapulmonary artery were taken from rabbit lungs and isometric tension measured during superfusion abt 37°C with physiological saline. Full or partial dose-response curves were obtained for 5-Hydroxytryptamine (5HT), Histamine (HIS), Norepinephrine (NE), Isoproterenol (IsoP), Arachidonic Acid (AA), PGA₁, PGB₁, PGB₂, PGE₁, PGE₂ and PGF₂α. In addition to pharmacological studies, length-tension properties of the segments utilized were examined and a qualitative analysis of smooth muscle content and orientation was undertaken. All prostaglandins elicited contractile effects, of varying magnitudes, at high doses. Prostaglandins A₁, E₁, and E₂ produced little or no contractile responses or slight relaxant activity in unstimulated PIPA and DIPA segments at low doses. 5HT contracted both PIPA and DIPA segments in a dose dependent manner, however, proximal segment maximal effects and sensitivity were significantly greater than those of the distal segment. Both PIPA and DIPA segments contracted to HIS and maximal effects were similar both segments. Mepyramine (10ˉ⁹M) antagonized contractile responses to HIS. In the presence of 10ˉ⁷M mepyramine, HIS produced dose dependent relaxation of precontracted PIPA and DIPA segments. Cimetidine (10ˉ⁵M) antagonized this relaxation indicating that HIS relaxant effects are mediated by H₂-HIS receptor stimulation in both segments. PIPA segments contracted in response to NE while the DIPA segment responded poorly or not at all suggesting a paucity of alpha adrenoreceptors in distal segments. IsoP produced dose dependent relaxation, that was antagonized by propranolol, of precontracted PIPA and DIPA segments. The dose related contractile response to AA was similar in both PIPA and DIPA segments. These studies indicate that regional differences exist in the response of rabbit IPA to some agonists.</p>