Baseline Vasomotor Tone Research Articles

Neuropeptide Y and neurovascular control in skeletal muscle and skin

Neuropeptide Y (NPY) is a ubiquitous peptide with multiple effects on energy metabolism, reproduction, neurogenesis, and emotion. In addition, NPY is an important sympathetic neurotransmitter involved in neurovascular regulation. Although early studies suggested that the vasoactive effects of NPY were limited to periods of high stress, there is growing evidence for the involvement of NPY on baseline vasomotor tone and sympathetically evoked vasoconstriction in vivo in both skeletal muscle and the cutaneous circulation. In Sprague-Dawley rat skeletal muscle, Y(1)-receptor activation appears to play an important role in the regulation of basal vascular conductance, and this effect is similar in magnitude to the alpha(1)-receptor contribution. Furthermore, under baseline conditions, agonist and receptor-based mechanisms for Y(1)-receptor-dependent control of vascular conductance in skeletal muscle are greater in male than female rats. In skin, there is Y(1)-receptor-mediated vasoconstriction during whole body, but not local, cooling. As with the NPY system in muscle, this neural effect in skin differs between males and females and in addition, declines with aging. Intriguingly, skin vasodilation to local heating also requires NPY and is currently thought to be acting via a nitric oxide pathway. These studies are establishing further interest in the role of NPY as an important vasoactive agent in muscle and skin, adding to the complexity of neurovascular regulation in these tissues. In this review, we focus on the role of NPY on baseline vasomotor tone in skeletal muscle and skin and how NPY modulates vasomotor tone in response to stress, with the aim of compiling what is currently known, while highlighting some of the more pertinent questions yet to be answered.

Abnormal in vivo response to sodium nitroprusside after porcine single lung transplantation.

The chronic increase of pulmonary vascular resistance after lung transplantation is only partly due to an active increase in baseline vasomotor tone, but the nature of the acute pulmonary hypertension after ischemia and reperfusion is not known. We studied the effects of sodium nitroprusside on pulmonary hemodynamics during reperfusion in porcine left lung allotransplants. In twelve pigs (weight: 18 to 24 kg) pulmonary arteries of the native and the transplanted lung were cannulated for right-heart bypass. The total blood flow was 2 L/min. Flow distribution between the lungs was measured at equal mean pulmonary artery pressure, and pulmonary vascular resistance at equal and constant flow-i.e., 1 L/min to each lung. After baseline measurements sodium nitroprusside (1, 3, and 9 microg/kg/min) was administered to six animals (SNP group). The control group (n=6) received an equal amount of the vehicle. After 30 min of discontinuation of the drug infusion, the schedule was repeated. In the transplanted lung, pulmonary vascular resistance decreased in all animals during the first hour of reperfusion. During the second drug infusion pulmonary vascular resistance was significantly lower in the SNP group compared with the control group only at the highest infusion rate of the drug (9 microg/kg/min), which also induced a 44% decrease in systemic vascular resistance. Arterial oxygen tension remained comparable in the two groups throughout the study. Our data suggest that other factors besides active vasoconstriction may contribute to the acute increase of pulmonary vascular resistance after lung transplantation.

Effects of hypoxia and vascular tone on endothelium-dependent and -independent responses in developing lungs

Both increases and decreases in endothelium-derived nitric oxide (EDNO) activity have been described in the developing pulmonary vasculature. We hypothesized that differences in baseline vasomotor tone and/or oxygen tension may contribute to this variability. Pulmonary arterial dose responses to endothelium-dependent and -independent vasodilators acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were measured in indomethacin-treated lungs of 1- to 2-day-old (2D) and 1-mo-old (1M) lambs. During 4% O2 ventilation, baseline pulmonary vascular resistance (PVR) and the dilator response to both ACh and SNP were greater in 2D lungs. However, when baseline PVR values were matched at both ages during either hypoxia or infusion of a thromboxane mimetic under normoxic conditions, developmental differences in ACh-induced vasodilation were minimal. Furthermore, hypoxia itself did not alter the responses to ACh in 2D lungs. In contrast, SNP caused greater vasodilation in 2D than in 1M lungs regardless of baseline PVR. These data and studies suggest that whereas high PVR enhances EDNO synthesis, responsiveness to ENDO decreases as synthesis of ENDO increases in developing lungs studied under basal conditions.

Role of endothelium-derived relaxing factor in reactive hyperemia in canine diaphragm.

We studied the effect of NG-nitro-L-arginine (L-NA) on reactive hyperemia in the vascularly isolated hemidiaphragm of anesthetized dogs pretreated with indomethacin. In nine animals, the diaphragm was autoperfused from the left femoral artery. Phrenic arterial flow was interrupted for 10-120 s during a control period and after 20 min of L-NA infusion (6 x 10(-4) M). Postocclusive flow and duration of hyperemia during the control period increased progressively with increasing occlusion duration. After L-NA infusion, baseline and postocclusive flow in response to all occlusions declined significantly compared with control values. However, when normalized as percentage of baseline flow, postocclusive flow remained similar to that during the control period. By comparison, the duration of reactive hyperemia was significantly shortened by L-NA infusion. In five animals, we repeated the same protocol during pump perfusion of the diaphragm at a fixed flow rate. L-NA infusion increased baseline and postocclusive phrenic resistance in response to all occlusion durations; however, postocclusive phrenic resistance as percentage of baseline remained similar to control values. In addition, hyperemia durations in response to 60- and 120-s occlusions were shortened significantly by L-NA infusion. We conclude that 1) endothelium-derived relaxing factor plays an important role in the regulation of baseline vasomotor tone in the diaphragm and 2) modulation of endothelium-derived relaxing factor release contributes to the reactive vasodilatory response to transient vascular occlusion in the diaphragm.

Abnormal responses to pulmonary vasodilators in conscious dogs after left lung autotransplantation.

We investigated the extent to which left lung autotransplantation (LLA) alters endothelium-dependent (bradykinin and acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilation in the pulmonary circulation of conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 3-4 wk post-LLA and in sham-operated controls. LLA resulted in a marked upward shift in the baseline LPQ relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The thromboxane analogue, U-46619, was used to acutely preconstrict the pulmonary circulation in control dogs, which shifted the control LPQ relationship to the same position measured post-LLA. Under these circumstances, bradykinin, acetylcholine, and nitroprusside caused pulmonary vasodilation in the control group, whereas these responses were either attenuated or reversed to vasoconstriction post-LLA. After acute preconstriction with U-46619 post-LLA, the pulmonary vasodilator responses to bradykinin and acetylcholine were again attenuated, but the response to nitroprusside was unaltered compared with control. These results indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is passively mediated and does not reflect an active increase in baseline vasomotor tone. Moreover, LLA results in an impairment in endothelium-dependent, but not endothelium-independent, pulmonary vasodilation in conscious dogs.

Cardiovascular responses of bluefish ( Pomatomus saltatrix) to epinephrine, phentolamine and atropine

1. Ventral aortic blood pressure and heart rate were recorded in bluefish ( Pomatomus saltatrix) that were either unanesthetized or anesthetized with tricaine methanesulfonate. 2. Epinephrine caused a dose-related increase of blood pressure. The competitive inhibitor phentolamine inhibited the epinephrine response. 3. Phentolamine lowered the resting blood pressure indicating a tonic adrenergic influence on baseline vasomotor tone. Phentolamine had no significant effect on heart rate. 4. Atropine increased heart rate, as in other teleosts, indicating there had been vagal inhibition of the heart rate at rest. 5. These pharmacological studies demonstrate that bluefish have parasympathetic influence on heart rate and can respond to adrenergically mediated vasomotor tone as do other teleosts.

Endothelin effects in isolated, perfused lamb lungs: role of cyclooxygenase inhibition and vasomotor tone

We have determined the sites of action of endothelin-1 (ET) in the lamb pulmonary circulation. The influence of cyclooxygenase inhibition and baseline vasomotor tone on ET effects was also studied. Lungs of 14 lambs (6-9 wk of age, 12.1 +/- 0.6 kg body wt) were isolated and perfused with blood. Group I lungs (n = 5) were untreated, group II lungs (n = 5) were treated with indomethacin to inhibit cyclooxygenase, and group III lungs (n = 4) were treated with indomethacin and a thromboxane A2 analogue, U-46619, to elevate vasomotor tone. All lungs were perfused with constant flow in zone 3, with left atrial and airway pressures being 8 and 6 cmH2O, respectively. We measured pulmonary arterial pressure and, by the micropuncture servo-null method, pressures in 20- to 50-microns diameter subpleural venules, both before and after each dose of ET was infused (50, 100, 250, and 500 ng/kg). Group I lungs, with high baseline vasomotor tone, exhibited a biphasic response to ET; 50-100 ng/kg of ET dilated both arteries and veins, whereas 500 ng/kg of ET constricted both arteries and veins. In group II lungs with low vasomotor tone, all doses of ET caused constriction of arteries only. In group III lungs (indomethacin treated with elevated vasomotor tone), 50-100 ng/kg of ET caused dilation of arteries and veins, whereas 500 ng/kg of ET induced constriction, this time only in arteries. We conclude that ET has both dilator and constrictor effects in arteries and veins of isolated, perfused lamb lungs. ET-induced arterial and venous dilation is dependent on initial vasomotor tone but not on cyclooxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Elimination of variable vasomotor tone in studies with repeated quantitative coronary angiography

In quantitative coronary angiographic studies, unintentional changes of coronary vasomotor tone may have a significant influence on the coronary artery diameters, thereby increasing the variability in the measurements. To obtain objective data on these measurement variabilities, two protocols were designed to assess the influences of ionic and nonionic radiographic contrast media on the mean diameters of angiographically normal coronary arteries. The vessel sizes were determined with the CAAS using automated edge detection techniques. In 21 patients (study no. I), coronary angiograms were taken in identical angiographic projections before (control), and immediately following several (at average 7) subsequent diagnostic dye injections administered over a period of about 7 min. The ionic contrast agent diatrizoate 76% induced a coronary dilation of 19 +/- 7% (mean +/- s.d., p less than 0.001; n = 10); the nonionic agent iopromide 370 increased the coronary artery diameters by only 6 +/- 4% (p less than 0.01; n = 11). In another 11 patients (study no. II) coronary angiograms were obtained using the nonionic contrast medium iopamidol 300 at 5, 8, 10 and 11 min after the control acquisition; this protocol was repeated in the same patients with diatrizoate 76%. With iopamidol, coronary diameter changes were not significant at any time; with diatrizoate, however, coronary dilation was measured at 10 min (2 +/- 2%; p less than 0.01) and at 11 min (10 +/- 3%; p less than 0.001). In a third study it was tested, whether standardization of coronary vasomotor tone (e.g. in coronary angiographic follow-up studies) is possible by the induction of a reproducible maximum coronary dilation with nitrocompounds. In 12 patients, the mean diameters of angiographically normal coronary segments were analyzed before and at various times after i.v. administration (over 4 min) of 0.025 mg SIN-1/kg bodyweight. Coronary dilation was maximal at 10 or 15 min after the onset of the SIN-1-infusion (29 +/- 5%; p less than 0.001). 0.8 mg nitroglycerin given s.l. at 15 min did not further dilate the coronary arteries (28 +/- 7%). One hour after SIN-1, coronary dilation still amounted to an average of 24 +/- 8% (p less than 0.001) and became 'maximal' again, when 0.8 mg nitroglycerin was again administered sublingually (28 +/- 8%; p less than 0.001). In conclusion, short-term variability of coronary vasomotor tone induced by ionic radiographic contrast media can be eliminated by the use of nonionic contrast agents and observation of injection intervals of at least 2 min. In quantitative coronary angiographic follow-up studies, as well as during acute interventions (e.g., PTCA), identical baseline vasomotor tone can be achieved by induction of the maximal coronary dilation using nitrocompounds.

Epidermal growth factor augments reactivity to angiotensin II in the rat pulmonary circulation.

To determine if epidermal growth factor (EGF), a vascular smooth muscle mitogen exhibiting systemic vasoactivity, causes constriction or dilation of the pulmonary vascular bed, this study evaluated the actions of EGF in isolated, buffer-perfused rat lungs and in isolated rat pulmonary arteries. In perfused rat lungs with baseline vasomotor tone, EGF administered at bolus doses of 10(-9) to 3 x 10(-7) M failed to exert either constrictor or dilator actions or to promote edema formation as evidenced by a constant lung wet-to-dry-weight ratio. Elevation of baseline tone with either prostaglandin (PG)F2 alpha or angiotensin II also failed to unmask an effect of EGF on pulmonary vascular resistance. In contrast to these negative observations, pretreatment with 5 x 10(-8) M EGF consistently augmented pressor responses evoked by angiotensin II. Constrictor responses to potassium chloride and to PGF2 alpha were unaffected by EGF pretreatment. In isolated rat extrapulmonary arteries, EGF provoked contraction in 40% of the preparations studied. Responsive vessels exhibited maximal EGF-induced contractions that were approximately 25% of that associated with angiotensin II and were characterized by an ED50 of 7 x 10(-8) M. Relaxant activity of EGF could not be demonstrated in isolated arterial preparations with normal resting tone or with tone elevated by addition of norepinephrine to the tissue bath. Endothelial denudation also failed to unmask contractile or relaxant effects of EGF. Similar to its actions in isolated, perfused rat lungs, EGF potentiated contractions of isolated pulmonary arteries induced by angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)

Microvascular pressures measured by micropuncture in isolated perfused lamb lungs.

To investigate the influence of vasomotor tone and vessel compliance on pulmonary segmental vascular resistance, we determined the longitudinal distribution of vascular pressures in 15 isolated blood perfused lungs of newborn lambs. We measured pulmonary arterial and left atrial pressures and by micropuncture the pressures in 20- to 80-micron-diam subpleural arterioles and venules, both before and after paralyzing the vasculature with papaverine hydrochloride. In five lungs we also determined the microvascular pressure profile during reverse perfusion. In lungs with baseline vasomotor tone, approximately 32% of the total pressure drop was in arteries, approximately 32% in microvessels, and approximately 36% in veins. With elimination of vasomotor tone, arterial and venous resistances decreased to one-fifth and one-half of base-line values, respectively, indicating that vasomotor tone contributed mainly toward arterial resistance. During reverse perfusion, the pressure drop in veins was similar to that in arteries during forward perfusion, suggesting that the compliance of arteries and veins is comparable. We conclude that vascular tone and compliance are important factors that determine the distribution of segmental vascular resistance in lungs of the newborn.

Vascular effects of cigarette smoke in isolated pig lungs.

To determine the local effects of cigarette smoke on the pulmonary vasculature, we measured pulmonary artery pressure--flow curves in isolated, blood-perfused pig lungs before and after 4 exposures to cigarette smoke. During each exposure, smoke was administered into the trachea for 3 to 4 min at a rate of 20 to 25 puffs/min and a puff volume of 35 to 50 ml with a smoking machine. During hypoxia (inspired PO2, 50 mmHg), when baseline vasomotor tone was high, cigarette smoke caused an acute transient vasodilation. During control (inspired PO2, 200 mmHg), when baseline tone was low, no significant effect was observed. In addition to this acute effect, cigarette smoke caused a depression of the pulmonary pressor response to hypoxia, which developed gradually during the course of the experiment. Indomethacin, at perfusate concentrations of 20 and 100 micrograms/ml, did not significantly alter the acute vasodilating effect of smoking, suggesting that prostaglandins synthesized by cyclooxygenase were not the mediators of this response. Indomethacin did, however, prevent the gradual depression of the pulmonary vasoconstrictor response to hypoxia.