Effect of vasoconstriction on longitudinal distribution of pulmonary vascular pressure and volume

We used an improved version of the low-viscosity bolus method to evaluate longitudinal (arterial-to-venous) differences in the sensitivity of the dog lung lobe vasculature to selected vasoconstrictor stimuli, including hypoxia, and serotonin, histamine, and norepinephrine infusions. This method revealed a bimodal distribution of local vascular resistance vs. cumulative vascular volume under the zone 3 conditions studied. Our interpretation of the two modes of relatively high resistance is that they correspond to high resistance per unit volume segments of the arteries and veins upstream and downstream from the relatively low resistance per unit volume capillary bed. Thus an increase in the height of the upstream and downstream modes of the resistance distribution suggests constriction in small arteries and veins, respectively. Horizontal displacement of the modes along the cumulative volume axis suggests changes in the distribution of volume among the arteries, veins, and capillary bed. By use of these criteria, the results are consistent with the concept that each of the vasoconstrictor stimuli studied had a different longitudinal response pattern. Hypoxia constricted mainly small arteries, whereas serotonin constricted small and large arteries. Histamine constricted large and small veins, and norepinephrine constricted large and small veins and arteries.     

Pulmonary vasodilator responses to vasoactive intestinal peptide in the cat

We investigated the effects of vasoactive intestinal peptide (VIP) in the feline pulmonary vascular bed under conditions of controlled pulmonary blood flow when pulmonary vascular tone was at base-line levels and when vascular resistance was elevated. Under base-line conditions, VIP caused small but significant reductions in lobar arterial pressure without affecting left atrial pressure. Decreases in lobar arterial pressure in response to VIP were greater and were dose related when lobar vascular resistance was increased by intralobar infusion of U 46619, a stable prostaglandin endoperoxide analogue. Acetylcholine and isoproterenol also caused significant decreases in lobar arterial pressure under base-line conditions, and responses to these agents were enhanced when lobar vascular tone was elevated. Moreover, when doses of these agents are expressed in nanomoles, acetylcholine and isoproterenol were more potent than VIP in decreasing lobar arterial pressure. Responses to VIP were longer in duration with a slower onset than were responses to acetylcholine or isoproterenol. Pulmonary vasodilator responses to VIP were unchanged by indomethacin, atropine, or propranolol. The present data demonstrate that VIP has vasodilator activity in the pulmonary vascular bed and that responses are dependent on the existing level of vasoconstrictor tone. These studies indicate that this peptide is less potent than acetylcholine or isoproterenol in dilating the feline pulmonary vascular bed and that responses to VIP are not dependent on a muscarinic or beta-adrenergic mechanism or release of a dilator prostaglandin.     

Comparison of the effects of prostaglandins F1alpha, F2alpha, F1beta, and F2beta on the canine pulmonary vascular bed.

The effects of four F series prostaglandins on the pulmonary vascular bed were compared under conditions of controlled pulmonary blood flow in the intact spontaneously breathing dog. PGF1alpha and PGF2alpha increased lobar arterial pressure whereas PGF1beta and PGF2beta had little if any effect when infused into the lobar artery. The increase in lobar arterial pressure in response to PGF1alpha and PGF2alpha was associated with a significant increase in lobar venous pressure but no change in left atrial pressure. These data indicate that PGF1alpha and PGF2alpha increase pulmonary vascular resistance by constricting lobar veins and vessels upstream to small veins, presumed to be small arteries. It is concluded that in the pulmonary vascular bed the configuration of the hydroxyl group at carbon 9 is an important determinant of pressor activity.     

Synthetic human adrenomedullin and ADM15-52 have potent short-lasting vasodilator activity in the pulmonary vascular bed of the cat

Responses to synthetic human adrenomedullin, a novel hypotensive peptide localized in several organ systems, including the lung, and the carboxy terminal 15-52 amino acid fragment of adrenomedullin (ADM15-52) were investigated in the pulmonary vascular bed of the intact-chest cat. Under constant flow conditions when baseline tone in the pulmonary vascular bed was raised to a high steady level, injections of adrenomedullin and ADM15-52 into the perfused lobar artery in doses of 0.1-1 nmol, caused significant doserelated decreases in lobar arterial pressure. Since left atrial pressure was unchanged, the decreases in lobar arterial pressure reflect decreases in pulmonary lobar vascular resistance. Adrenomedullin and ADM15-52 exhibited similar vasodilator activity and were approximately 3-fold more potent than bradykinin in the pulmonary vascular bed of the cat. Pulmonary vasodilator responses to adrenomedullin and ADM15-52 were rapid in onset and laster for 150–200 sec, depending on the dose of the peptide injected. The present results demonstrate that synthetic human adrenomedullin and ADM15-52 possess potent, short-lasting vasodilator activity in the pulmonary vascular bed of the cat and suggest that amino acids 15-52 in the peptide are important for the expression of vasodilator activity in the pulmonary vascular bed of the cat.     

Differential effects of prostaglandins A1 and A2 on pulmonary vascular resistance in the dog.

The effects of PGA1 and PGA2 were studied in the canine pulmonary vascular bed. Infusion of PGA1 into the lobar artery decreased lobar arterial and venous pressure but did not change left atrial pressure. In contrast, PGA2 infusion increased lobar arterial and venous pressure and the effects of this substance were similar in experiments in which the lung was perfused with dextran or with blood. These data indicate that under conditions of controlled blood flow PGA1 decreases pulmonary vascular resistance by dilating intrapulmonary veins and to a lesser extent vessels upstream to the small veins, presumably small arteries. The present data show that PGA2 increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream vessels. The predominant effect of PGA2 was on upstream vessels and the pressor effect was not due to interaction with formed elements in the blood or platelet aggregation.     

Influence of cyclooxygenase blockade on responses to isoproterenol, bradykinin and nitroglycerin in the feline pulmonary vascular bed

We investigated the effect of indomethacin on responses to isoproterenol, bradykinin and nitroglycerin in the feline pulmonary vascular bed when pulmonary vascular resistance was actively increased by infusion of U46619 in order to determine if vasodilator responses to these agents were dependent on the integrity of the cyclooxygenase pathway. Since pulmonary blood flow left atrial pressure were held constant, changes in lobar arterial pressure directly reflect changes in lobar vascular resistance. Intralobar injections of isoproterenol, bradykinin, and nitroglycerin decreased lobar arterial pressure in a dose-related manner. Pulmonary vasodilator responses to the lower and midrange doses of bradykinin and nitrogylcerin were unchanged in the presence of indomethacin whereas pulmonary responses to the highest doses of nitroglycerin and bradykinin were increased by cyclooxygenase blockade. In contrast, pulmonary vasodilator responses to isoproterenol were significantly attenuated in the presence of propranolol, whereas pulmonary vasodilator responses to bradykinin and nitroglycerin were unchanged after beta blockade. The present data indicate that isoproterenol, bladykinin, and nitroglycerin have significant vasodilator activity in the cat when pulmonary vascular tone is actively increased. These data suggest that the formation of vasodilator cyclooxygenase products such as PGI₂ do not mediate vasodilator responses to isoproterenol, bradykinin, and nitroglycerin in the feline pulmonary vascular bed.     

Influence of cyclooxygenase blockade on responses to isoproterenol, bradykinin and nitroglycerin in the feline pulmonary vascular bed

We investigated the effect of indomethacin on responses to isoproterenol, bradykinin and nitroglycerin in the feline pulmonary vascular bed when pulmonary vascular resistance was actively increased by infusion of U46619 in order to determine if vasodilator responses to these agents were dependent on the integrity of the cyclooxygenase pathway. Since pulmonary blood flow and left atrial pressure were held constant, changes in lobar arterial pressure directly reflect changes in lobar vascular resistance. Intralobar injections of isoproterenol, bradykinin, and nitroglycerin decreased lobar arterial pressure in a dose-related manner. Pulmonary vasodilator responses to the lower and midrange doses of bradykinin and nitroglycerin were unchanged in the presence of indomethacin whereas pulmonary responses to the highest doses of nitroglycerin and bradykinin were increased by cyclooxygenase blockade. In contrast, pulmonary vasodilator responses to isoproterenol were significantly attenuated in the presence of propranolol, whereas pulmonary vasodilator responses to bradykinin and nitroglycerin were unchanged after beta blockade. The present data indicate that isoproterenol, bradykinin, and nitroglycerin have significant vasodilator activity in the cat when pulmonary vascular tone is actively increased. These data suggest that the formation of vasodilator cyclooxygenase products such as PGI2 do not mediate vasodilator responses to isoproterenol, bradykinin, and nitroglycerin in the feline pulmonary vascular bed.     

Phasic capillary pressure determined by arterial occlusion in intact dog lung lobes

In six open-chest dogs, electrocardiogram- (ECG) controlled pulmonary arterial occlusion was performed during the control period and during the infusions of serotonin and histamine. A temporal series of instantaneous pulmonary capillary pressure and the longitudinal distributions of vascular resistance and compliance were evaluated in the intact left lower lung lobe. In the control period, we found a significant phasic variation of pulmonary capillary pressure (Pc) with the cardiac cycle. The ratio of arterial to venous resistances (Ra/Rv) was 6:4, and the ratio of arterial to capillary compliances (Ca/Cc) was 1:11. During the infusions of serotonin and histamine, Pc showed similar phasic variations, despite significant hemodynamic changes induced by these agents. Serotonin predominantly increased Ra, whereas histamine predominantly increased Rv. The ratio of Rv to the total resistance decreased significantly from 0.42 to 0.32 during the infusion of serotonin and increased significantly to 0.62 during the infusion of histamine. The data suggest that phasic Pc determined by ECG-controlled arterial occlusion reflects the pulsatility in the pulmonary microvascular bed under control conditions and after alterations of the pulmonary vascular resistance by serotonin and histamine.     

Hepatic venous resistance site in the dog: localization and validation of intrahepatic pressure measurements

Intrahepatic pressure (9.4 +/- 0.3 mmHg; 1 mmHg = 133.32 Pa), measured proximal to a hepatic venous resistance site, was insignificantly different from portal venous pressure (9.6 +/- 0.4 mmHg). This lobar venous pressure is not wedged hepatic venous pressure as it is measured from side holes in a catheter with a sealed tip. Validation of the lobar venous pressure measurement was done in a variety of ways and using different sizes and configurations of catheters. The site of hepatic venous resistance in the dog is localized to a narrow sphincterlike region about 0.5 cm in length and within 1-2 cm (usually within 1 cm) of the junction of the vena cava and hepatic veins. Sinusoidal and portal venous resistance appears insignificant in the basal state and large increases in liver blood volume (histamine infusion or passive vena caval occlusion) or large decreases in liver blood volume (passive vascular occlusion) do not alter the insignificant pressure gradient between portal and lobar venous pressures. Norepinephrine infusion (1.25 microgram X kg-1 X min-1 intraportal) and hepatic sympathetic nerve stimulation (10 Hz) led to a significantly greater rise in portal venous pressure than in lobar venous pressure, indicating some presinusoidal (and (or) sinusoidal) constriction and this indicates that lobar venous pressure cannot be assumed under all conditions to accurately reflect portal pressure. However, most of the rise in portal venous pressure induced by intraportal infusion of norepinephrine or nerve stimulation and virtually all of the pressure rise induced by histamine could be attributed to the postsinusoidal resistance site.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative responses to endothelin-2 and sarafotoxin 6b in the pulmonary vascular bed of the cat

Pulmonary vascular responses to endothelin-2 and sarafotoxin 6b were investigated in the feline pulmonary vascular bed under natural flow and constant flow conditions. Injections of endothelin-2 and sarafotoxin 6b in a dose of 0.3 nmol/kg iv increased pulmonary arterial and left atrial pressures and cardiac output, and caused a biphasic change in calculated pulmonary vascular resistance. Endothelin-2 caused a biphasic change in systemic arterial pressure, while sarafotoxin 6b only decreased arterial pressure. Under constant flow conditions in the intact-chest cat, injections of endothelin-2 and sarafotoxin 6b in doses of 0.1-1 nmol into the perfused lobar artery increased lobar arterial pressure in a dose-related manner but were less potent than the thromboxane A2 mimic, U46619. An ET analog with only the Cys1-Cys15 disulfide bond and an amidated carboxy terminus had no significant activity in the pulmonary vascular bed. The present data show that endothelin-2 and sarafotoxin 6b have significant vasoconstrictor activity in the pulmonary vascular bed of the cat.     

A fractal continuum model of the pulmonary arterial tree.

The extant morphometric data from the intrapulmonary arteries of dog, human, and cat lungs produce graphs of the log of the vessel number, (N) or length (l) in each level vs. the log of the mean diameter (D) in each level that are sufficiently linear to suggest that a scale-independent self-similar or fractal structure may underlie the observed relationships. These data can be correlated by the following formulas: Nj = a1Dj-beta 1, and lj = a2Dj beta 2, where j denotes the level (order or generation) number measured from the largest vessel at the entrance to the arterial tree to the smallest vessel at the entrance to the capillary bed. With the hemodynamic resistance (R) represented by Rj = 128 microliterj/(Nj pi Dj4) and the vascular volume (Q) by Qj = Nj pi Dj2lj/4, the continuous cumulative distribution of vascular resistance (Rcum) vs. cumulative vascular volume (Qcum) (where Rcum and Qcum represent the total resistance or volume, respectively, upstream from the jth level) can be calculated from [formula: see text] where r = Dj/Dj+1 is a constant independent of j. Analogous equations are developed for the inertance and compliance distributions, providing simple formulas to represent the hemodynamic consequences of the pulmonary arterial tree structure.     

Pulmonary vascular compliance and viscoelasticity

When dog lung lobes were perfused at constant arterial inflow rate, occlusion of the venous outflow (VO) produced a rapid jump in venous pressure (Pv) followed by a slower rise in both arterial pressure (Pa) and Pv. During the slow rise Pa(t) and Pv(t) tended to converge and become concave upward as the volume of blood in the lungs increased. We compared the dynamic vascular volume vs. pressure curves obtained after VO with the static volume vs. pressure curves obtained by dye dilution. The slope of the static curve (the static compliance, Cst) was always larger than the slope of the dynamic curve (the dynamic compliance, Cdyn). In addition, the Cdyn decreased with increasing blood flow rate. When venous occlusion (VO) was followed after a short time interval by arterial occlusion (AO) such that the lobe was isovolumic, both Pa and Pv fell with time to a level that was below either pressure at the instant of AO. In an attempt to explain these observations a compartmental model was constructed in which the hemodynamic resistance and vascular compliance were volume dependent and the vessel walls were viscoelastic. These features of the model could account for the convergence and upward concavity of the Pa and Pv curves after VO and the pressure relaxation in the isovolumic state after AO, respectively. According to the model analysis, the difference between Cst and Cdyn and the flow dependence of Cdyn are due to wall viscosity and volume dependence of compliance, respectively. Model analysis also suggested ways of evaluating changes in the viscoelasticity of the lobar vascular bed. Hypoxic vasoconstriction that increased total vascular resistance also decreased Cst and Cdyn and appeared to increase the vessel wall viscosity.     

Nisoldipine inhibits vasoconstrictor responses in the cat pulmonary vascular bed

The influence of nisoldipine, a dihydropyridine calcium entry antagonist, on vascular resistance and vasoconstrictor responses was investigated in the feline pulmonary vascular bed under conditions of controlled blood flow. The calcium channel blocking agent caused a small reduction in lobar vascular resistance and blocked pulmonary vasoconstrictor responses to BAY K 8644, an agent which promotes calcium entry. The calcium entry blocking agent also reduced pulmonary vasoconstrictor responses to methoxamine and to BHT 933, alpha 1- and alpha 2-adrenoceptor agonists, and to U 46619, an agent which mimics the actions of thromboxane A2. Although there was a marked difference in vasoconstrictor potency in the pulmonary vascular bed, responses to the thromboxane mimic and to the alpha 1- and alpha 2-adrenoceptor agonists were reduced by approximately the same extent. The increases in systemic arterial pressure in response to BAY K 8644, methoxamine, and BHT 933 were also reduced by nisoldipine, and the calcium entry antagonist reduced systemic arterial pressure and systemic vascular resistance. The results of the present study suggest that an extracellular source of calcium is required for the maintenance of vascular tone and for the expression of vasoconstrictor responses, resulting from activation of alpha 1- and postjunctional alpha 2-adrenoceptors and thromboxane receptors in the feline pulmonary vascular bed.     

Kinetic measurements of gas exchange in the intact pulmonary microcirculation.

The kinetics of gas exchange are monitored in an isolated perfused lung preparation contained within a plethysmograph. The lungs are perfused with buffer, and there is no gas exchange until a 2.0-ml bolus of reactant is injected into the perfusion system. Subsequent gas exchange produces a pressure transient that is related to the corresponding volume of exchanged gas. The observed rate of volume change is the result of two separate processes: 1) the rate of gas exchange during transit through the capillary bed and 2) the distribution of vascular transit times between the point of injection and the capillary bed. The latter is assessed by a control injection containing a dissolved inert gas that is liberated in the alveoli as the bolus enters the capillary bed. Analysis of the experimental curves permits the separation of these two processes. A model of exchange kinetics indicates that this method has the capability of measuring kinetic events occurring during gas exchange in the microcirculation under physiological conditions.     

Pulmonary vasodilation with structurally altered pulmonary vessels and pulmonary hypertension

To evaluate pulmonary vasodilation in a structurally altered pulmonary vascular bed, we gave endothelium-dependent (acetylcholine) and endothelium-independent [sodium nitroprusside, prostaglandin I2 (PGI2)] vasodilators in vivo and to isolated lobar pulmonary arteries from neonatal calves with severe pulmonary hypertension. Acetylcholine, administered by pulmonary artery infusion, decreased pulmonary arterial pressure from 120 +/- 7 to 71 +/- 6 mmHg and total pulmonary resistance from 29.4 +/- 2.6 to 10.4 +/- 0.9 mmHg.l-1.min without changing systemic arterial pressure (90 +/- 5 mmHg). Although both sodium nitroprusside and PGI2 lowered pulmonary arterial pressure to 86 +/- 4 and 96 +/- 4 mmHg, respectively, they also decreased systemic arterial pressure to 65 +/- 4 and 74 +/- 3 mmHg, respectively. Neither sodium nitroprusside nor PGI2 was as effective as acetylcholine at lowering total pulmonary resistance (18.0 +/- 3.6 and 19.1 +/- 2.2 mmHg.l-1.min, respectively). Right-to-left cardiac shunt through the foramen ovale was decreased by acetylcholine from 1.6 +/- 0.4 to 0.1 +/- 0.2 l/min but was not changed by sodium nitroprusside or PGI2. Isolated lobar pulmonary arteries from pulmonary hypertensive calves did not relax in response to acetylcholine, whereas isolated pulmonary arteries from age-matched control calves did relax in response to acetylcholine. Control and pulmonary hypertensive lobar pulmonary arteries relaxed equally well in response to sodium nitroprusside. We concluded that acetylcholine vasodilation was impaired in vitro in isolated lobar pulmonary arteries but was enhanced in vivo in resistance pulmonary arteries in neonatal calves with pulmonary hypertension.     

Localization of the sites of pulmonary vasomotion by use of arterial and venous occlusion

In this study, we present a new approach for using the pressure vs. time data obtained after various vascular occlusion maneuvers in pump-perfused lungs to gain insight into the longitudinal distribution of vascular resistance with respect to vascular compliance. Occlusion data were obtained from isolated dog lung lobes under normal control conditions, during hypoxia, and during histamine or serotonin infusion. The data used in the analysis include the slope of the arterial pressure curve and the zero time intercept of the extrapolated venous pressure curve after venous occlusion, the equilibrium pressure after simultaneous occlusion of both the arterial inflow and venous outflow, and the area bounded by equilibrium pressure and the arterial pressure curve after arterial occlusion. We analyzed these data by use of a compartmental model in which the vascular bed is represented by three parallel compliances separated by two series resistances, and each of the three compliances and the two resistances can be identified. To interpret the model parameters, we view the large arteries and veins as mainly compliance vessels and the small arteries and veins as mainly resistance vessels. The capillary bed is viewed as having a high compliance, and any capillary resistance is included in the two series resistances. With this view in mind, the results are consistent with the major response to serotonin infusion being constriction of large and small arteries (a decrease in arterial compliance and an increase in arterial resistance), the major response to histamine infusion being constriction of small and large veins (an increase in venous resistance and a decrease in venous compliance), and the major response to hypoxia being constriction of the small arteries (an increase in arterial resistance). The results suggest that this approach may have utility for evaluation of the sites of action of pulmonary vasomotor stimuli.     

N omega-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin.

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor (EDRF) production, on vascular tone and responses were investigated in the pulmonary vascular bed of the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was elevated with U-46619, intralobar injections of acetylcholine, bradykinin, sodium nitroprusside, isoproterenol, prostaglandin E1 (PGE1), lemakalim, and 8-bromo-guanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) dilated the pulmonary vascular bed. Intravenous administration of L-NAME elevated lobar arterial and systemic arterial pressures without altering left atrial pressure. When U-46619 was infused after L-NAME to raise lobar arterial pressure to levels similar to those attained during the control period, vasodilator responses to acetylcholine and bradykinin were reduced significantly, whereas responses to PGE1, lemakalim, and 8-bromo-cGMP were not altered, and responses to nitroprusside were increased. There was a small effect on the response to the highest dose of isoproterenol, and pressor responses to BAY K 8644 and angiotensin II were not altered. These results are consistent with the hypothesis that EDRF production may involve the formation of nitric oxide or a nitroso compound from L-arginine and that EDRF production may have a role in the regulation of tone and in the mediation of responses to acetylcholine and bradykinin in the pulmonary vascular bed of the cat.     

Hypoxia-induced alterations of norepinephrine vascular reactivity in isolated perfused cat lung

Past work in the isolated perfused cat lung has shown that acute hypoxia (H) changes the response to norepinephrine (NE) from vasoconstriction to vasodilation but has no effect on the response to serotonin (S). These results could be related to the increase in pulmonary arterial pressure or vascular resistance during the hypoxic pressor response or a direct effect of H. We addressed this question, in the same preparation, by comparing responses to NE under four conditions in each experimental animal (n = 12): 1) NE infused during normoxia; 2) NE infused after vascular resistance (Rpv) was increased with serotonin; 3) NE infused after Rpv was increased by H; 4) NE infused after lobar pressure was raised by an increase in flow (P/F). PO2 values during H were varied (27-56 Torr). S and H produced a 137 +/- 35 and 43 +/- 8% delta Rpv increase in lobar vascular resistance, respectively. P/F increased lobar pressure 91 +/- 10%. Only NE infusion during H demonstrated significant differences in lobar pressure and Rpv compared with control normoxic periods. There was no correlation between responses to NE during S, H, and P/F and degree to which each stimulus increased Rpv or lobar pressure (r = 0.003, 0.28, 0.24). A significant relationship between response to NE during H vs. PO2 during H was observed (r = 0.78; P less than 0.001). In a subset of animals, we repeated the infusion of NE during H and P/F post-beta-blockade. The decrease in vascular response to NE during H and the correlation of PO2 with NE response were abolished (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)     

L-NAME enhances responses to atrial natriuretic peptide in the pulmonary vascular bed of the cat.

This study investigated the hypothesis that atrial natriuretic peptide (ANP) responses are mediated by particulate guanylate cyclase in the pulmonary vascular bed of the cat. When tone in the pulmonary vascular bed was raised to a high steady level with the thromboxane mimic U-46619, injections of ANP caused dose-related decreases in lobar arterial pressure. After administration of HS-142-1, an ANP-A- and ANP-B-receptor antagonist, vasodilator responses to ANP were reduced. The nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) enhanced ANP vasodilator responses, suggesting that inhibition of NO modulates ANP responses. L-NAME administration with constant 8-bromo-cGMP infusion attenuated the increased vasodilator response to ANP, suggesting that supersensitivity to ANP occurs upstream to activation of a cGMP-dependent protein kinase. In pulmonary arterial rings, ANP produced concentration-related vasorelaxant responses with and without endothelium. Methylene blue, L-NAME, or N(omega)-monomethyl-L-arginine did not alter ANP vasorelaxant responses. These data show that ANP supersensitivity observed in the intact pulmonary vascular bed is not seen in isolated pulmonary arterial segments, suggesting that it may only occur in resistance vessel elements. These results suggest that ANP responses occur through activation of ANP-A and/or -B receptors in an endothelium-independent manner and are modulated by NO in resistance vessel elements in the pulmonary vascular bed of the cat.     

Regulation of muscle sympathetic nerve activity after bed rest deconditioning

Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether changes in autonomic function might produce this effect, we developed stimulus-response curves relating limb vascular resistance, muscle sympathetic nerve activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven subjects before and after 18 days of -6 degrees head-down bed rest. Both lower body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and 30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P = 0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest deconditioning produced hypovolemia, causing a shift in operating point on the stimulus-response curve. The relationship between limb vascular resistance and MSNA was not significantly altered after bed rest. We conclude that bed rest deconditioning does not alter reflex control of MSNA, but may produce orthostatic intolerance through a combination of hypovolemia and cardiac atrophy.