Pulmonary Vascular Smooth Muscle Tone Research Articles

Control of pulmonary vascular smooth muscle tone by sarcoplasmic reticulum Ca2+ pump blockers: thapsigargin and cyclopiazonic acid.

The effect of thapsigargin (TG) and cyclopiazonic acid (CPA) on the mechanical activity of the rat pulmonary artery were investigated. In chemically (beta-escin)-skinned arterial strips, application of TG (0.1-1 microM) or CPA (0.5-10 microM) prior and throughout the loading procedure of the internal Ca2+ stores (0.3 microM free Ca2+ ions for 8-10 min) concentration dependently inhibited the subsequent contractile response induced by noradrenaline (NA, 10 microM) or caffeine (25 mM). In intact strips repeatedly incubated in a Ca(2+)-containing solution (2.5 mM for 10 min), followed by incubation in a Ca(2+)-free solution 12 min before NA-stimulation, TG and CPA not only inhibited the NA-induced contraction but also increased the tension which appeared during the exposure time to Ca2+. The two phenomena developed with similar time courses. The increase in tension during the readmission of Ca2+ ions was not antagonized by verapamil (10 microM) or nifedipine (1 microM) but was blocked by La3+ (50 microM) and Co2+ (1 mM) ions. The amplitude of the verapamil-insensitive TG (or CPA)-induced contraction was dependent on the external [Ca2+] [0.1-10 mM, concentration for half maximal effect (EC50) = 0.85 mM], not modified by the reduction of the external [Na+] (from 130 to 10 mM) and decreased by depolarization of the strip using K(+)-rich (30-120 mM) solutions. Under the latter condition, 38 +/- 9 and 83 +/- 4% reduction (n = 5) was observed in the presence of 60 and 120 mM K+ respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous Basal Formation of Endothelium-Derived Relaxing Factor and Muscle-Derived Relaxing Factor, Both of Which Are Nitric Oxide

The objective of this study was to ascertain the role of both the vascular endothelium and smooth muscle in the continous regulation of pulmonary vascular smooth muscle tone. Isolated rings of endothelium-intact and endothelium-denuded bovine pulmonary artery and vein were studied. Competitive inhibitors of nitric oxide (NO) synthase activity (N G -amino-L-arginine and N G -nitro-L-arginine) or NO action (hemoglobin) contracted arterial and venous rings in the presence or absence of endothelium, and contractile responses were accompanied by marked decreases in endogenous guanosine-3', 5'-cyclic monophosphate (cyclic GMP) levels.

Continuous Basal Formation of Endothelium-Derived Relaxing Factor and Muscle-Derived Relaxing Factor, Both of Which Are Nitric Oxide

Summary: The objective of this study was to ascertain the role of both the vascular endothelium and smooth muscle in the continuous regulation of pulmonary vascular smooth muscle tone. Isolated rings of endothelium-intact and endothelium-denuded bovine pulmonary artery and vein were studied. Competitive inhibitors of nitric oxide (NO) synthase activity (NG-amino-l-arginine and NG-nitro-l-arginine) or NO action (hemoglobin) contracted arterial and venous rings in the presence or absence of endothelium, and contractile responses were accompanied by marked decreases in endogenous guanosine-3′,5′-cyclic monophosphate (cyclic GMP) levels. l-Arginine failed to relax freshly isolated arterial rings but caused endothelium-independent relaxation of, and elevation of cyclic GMP levels in, rings that had been incubated for 16-24 h to deplete rings of endogenous l-arginine. Incubation of endothelium-denuded arterial rings with lipopolysaccharide or interleukin-1 for 16 h caused a marked cycloheximide-sensitive tissue accumulation of cyclic GMP and nitrite (NO2-). These studies indicate that both the pulmonary vascular endothelium and smooth muscle continually release NO in quantities sufficient to maintain a decreased vascular smooth muscle tone.

Redox Status and Pulmonary Vascular Reactivity

Oxygen radicals are produced during oxidative metabolism in proportion to the tissue oxygen tension. The studies reported here have shown that oxygen radicals or the sulfhydryl oxidant, diamide, caused pulmonary vasodilatation in the isolated perfused rat lung. Could oxygen radicals play a role in the physiologic control of pulmonary vascular smooth muscle tone?

Relaxant activity of atriopeptins in isolated guinea pig airway and vascular smooth muscle

Atriopeptins are circulating peptide hormones which are secreted by atrial tissue and act at the kidney. Because the atriopeptins survive passage through the pulmonary circulation, they also may be involved in the modulation of airway or pulmonary vascular smooth muscle tone. Using in vitro organ bath techniques, atriopeptins were found to induce potent concentration-dependent relaxation of isolated guinea pig trachea, and pulmonary artery with a rank order of potency: atriopeptin III > atriopeptin II > atriopeptin I. Atriopeptin-induced smooth muscle relaxation was observed to be a direct response since it was not mediated by activation of relaxant VIP receptors, beta-adrenergic receptors, or H 2 receptors nor affected by cyclooxygenase inhibition or denuding of the vasculature or trachea of endothelial and epithelial cells. The time course of atriopeptin II-induced relaxation of the plumonary artery was transient in contrast to the prolonged relaxations on the trachea. The transient relaxant responses of atriopeptin II on pulmonary artery were not due to metabolism of atriopeptin II to atriopeptin I by angiotensin-converting enzyme since pretreatment with captopril did not augment the response. These results seem to indicate that distinct atriopeptin receptors may exist in airway and pulmonary arterial smooth muscle and that activation of these relaxant receptors may play an important role in the regulation of pulmonary vascular and bronchomotor tone.

Effects of high frequency oscillatory ventilation compared to conventional ventilation upon pulmonary vascular prostanoid production in neonatal piglets

In order to investigate the possibility that high-frequency oscillatory ventilation (HFO) might preferentially stimulate intrapulmonary prostacyclin (PGI 2) synthesis thereby decreasing pulmonary vascular smooth muscle tone, we determined pulmonary prostacyclin and thromboxane production in neonatal piglets ventilated by conventional means and by HFO (8 Hz). There was no detectable release of prostacyclin or thromboxane into blood passing through the lungs (i.e., pulmonary arterial concentrations were greater than aortic concentrations) during ventilation by conventional means or during HFO. Furthermore, there were no differences between the two modes of ventilation in cardiac output, systemic or pulmonary vascular resistance, or pulmonary vascular response to hypoxia/hypercapnia. We conclude that HFO does not stimulate pulmonary prostacyclin production and does not affect pulmonary vascular resistance or the pulmonary vasoconstriction associated with alveolar hypoxia/hypercapnia when compared to conventional ventilation in anesthetized newborn piglets.

Pulmonary vasoactivity of lung endocrine cell-related peptides

Lung endocrine-like cells are believed to contain three immunohistochemically distinct peptides: bombesin, calcitonin, and Leu-enkephalin. Because these peptides exhibit smooth muscle stimulatory or inhibitory activity in some tissues, it has been suggested that their release from endocrine-like cells may influence airway or pulmonary vascular smooth muscle tone. To determine whether lung endocrine cell-related peptides could exert a regulatory influence in the pulmonary circulation, we evaluated their ability to constrict or dilate the vasculature of isolated perfused rat lungs. Neither bombesin nor calcitonin exhibited any pulmonary vascular effects. However, Leu-enkephalin provoked dose-dependent pulmonary vasoconstriction. These results suggest that Leu-enkephalin released from lung endocrine-like cells could be involved with regulation of pulmonary vascular tone.

Relaxant effects of vasoactive intestinal peptide and bethanechol in cat intrapulmonary artery

The relaxant actions of vasoactive intestinal peptide (VIP) and bethanechol were examined on ring segments of intrapulmonary artery (IPA) isolated from cat lung. On a molar basis, VIP was 75 times more potent than bethanechol; however, VIP was less efficacious than bethanechol in reversing phenylephrine induced tone. Responses to VIP were unaffected by pretreatment of the tissues with atropine, indomethacin or avian pancreatic polypeptide. These results suggest that VIP may participate in the regulation of pulmonary vascular smooth muscle tone through a potent relaxant action that occurs independent of muscarinic cholinergic receptor activation or liberation of prostaglandins.

Direct pulmonary vascular responses to prostaglandins in the conscious newborn lamb.

The effects of prostaglandins PGD2, PGE1, PGE2, PGF2 alpha, and PGI2 on pulmonary vascular tone were investigated in normoxic and hypoxic unsedated newborn lambs with chronically implanted flow probes around right and left pulmonary arteries. Prostaglandins were injected into only one pulmonary artery, and direct effects of the compounds were determined by comparing the flow changes in the injected vs. the uninjected lung. PGD2 and PGF2 alpha were direct pulmonary vasoconstrictors, whereas PGE1, PGE2 and PGI2 were direct pulmonary dilators. Hypoxia augmented the vasodilation of PGE1 and PGI2 and diminished the constriction of PGD2 and PGF2 alpha; it also lowered the threshold for PGI2-induced dilation. While the E-type prostaglandins and PGI2 were both local dilators, they differed in that the systemic dilatory effects of the E-type agents exceeded their pulmonary effects, whereas the opposite occurred with PGI2. These results demonstrate that prostaglandins can act locally on pulmonary vascular smooth muscle tone in vivo and that the level of oxygenation or base-line vascular tone influences the pulmonary vascular responses to the PGs. Among the dilator prostaglandins, PGI2 appears to be more effective on the pulmonary rather than the systemic vascular bed under hypoxic conditions.