Quantitative assessment of hemoglobin-induced endothelial barrier dysfunction.

Hemoglobin (Hb)-based O2 carriers (HBOC) are undergoing extensive development as potential "blood substitutes." A major problem associated with these molecules is an increase in microvascular permeability and peripheral vascular resistance. In this paper, we utilized bovine lung microvascular endothelial cell monolayers and simultaneously measured Hb-induced changes in transendothelial electrical resistance, diffusive albumin permeability, and diffusive Hb permeability (PDH) for three forms of Hb: natural tetrameric human Hb-A and two polymerized recombinant HBOCs containing alpha-human and beta-bovine chains designated Hb-Polytaur (molecular mass: 500 kDa) and Hb-(Polytaur)n (molecular mass: approximately 1,000,000 Da), respectively.

Comparative responses to alpha,beta-methylene-ATP in cat pulmonary, mesenteric, and hindquarter vascular beds.

Responses to the P2X-purinoceptor agonist alpha,beta-methylene-ATP (alpha,beta-MeATP) were investigated in the pulmonary, hindquarter, and mesenteric vascular beds in the cat. Under constant-flow conditions, injections of alpha,beta-MeATP caused dose-related increases in perfusion pressure in the pulmonary and hindquarter beds and a biphasic response in the mesenteric circulation. In the pulmonary vascular bed, the order of potency was alpha,beta-MeATP > U-46619 > angiotensin II, whereas, in the hindquarters, the order of potency was angiotensin II > U-46619 > alpha,beta-MeATP.

An analysis of responses to levosimendan in the pulmonary vascular bed of the cat.

Unlabelled: Calcium-sensitizing drugs, such as levosimendan, are a novel class of drug therapy for heart failure. We investigated the hypothesis that levosimendan is a pulmonary vasodepressor mediated through inhibition of phosphodiesterase, adenosine triphosphate (ATP)-dependent potassium channels, or both. We investigated responses to the calcium sensitizer levosimendan in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure when lobar arterial pressure was increased to a high steady level with the thromboxane A(2) analog U-46619.

Inhibitory Effects of LY301875 on Responses to Angiotensin Peptides in Pulmonary Vascular Bed of the Cat.

The effects of the nonpeptide angiotensin receptor antagonist LY301875 on responses to angiotensin II, angiotensin III, and angiotensin IV were investigated in the pulmonary vascular bed of the intact cat chest. Under conditions of controlled blood flow, injections of the angiotensin peptides into the perfused lobar artery caused dose-related increases in lobar arterial pressure, and LY301875 decreased pressor responses to angiotensin II, angiotensin III, and angiotensin IV. The duration of the blockade was related to the dose of the antagonist, and LY301875 had no significant effect on pressor responses to U-46619, norepinephrine, serotonin or BAY K 8644.

Influence of HOE 140, A Bradykinin Receptor Antagonist, in the Isolated Mesenteric Vascular Bed of the Rat.

The inhibitory effects of HOE 140 (D-Arg-[Hyp(3),Thi(5),D-Tic(7), Oic(8)]bradykinin), a novel bradykinin B(2)-receptor antagonist, on mesenteric vascular bed vasodilator responses to bradykinin (BK) were investigated under constant-flow conditions in the isolated blood-perfused rat mesenteric vascular bed. During baseline conditions, injections of BK produced dose-related decreases in mesenteric arterial perfusion pressure which were reproducible with respect to time. HOE 140, in a dose of 50 &mgr;g/kg intravenously, decreased vasodilator responses to BK but had no significant effect on mesenteric vasodilator responses to albuterol, acetylcholine, levcromakalim, or to nitroglycerin.