Search

The article offers information on ice extent anomalies in 2015. Topics discussed key variables used to describe the state of the ice cover including sea ice extent, the age of sea ice serves as an indicator for physical properties of ice which describe its surface roughness melt pond coverage, and thickness, and the sea ice thickness and volume.

A Lagrangian snow-evolution model (SnowModel-LG) was used to produce daily, pan-Arctic, snow-on-sea-ice, snow property distributions on a 25 × 25-km grid, from 1 August 1980 through 31 July 2018 (38 years). The model was forced with NASA's Modern Era Retrospective-Analysis for Research and Applications-Version 2 (MERRA-2) and European Centre for Medium-Range Weather Forecasts (ECMWF) ReAnalysis-5th Generation (ERA5) atmospheric reanalyses, and National Snow and Ice Data Center (NSIDC) sea ice parcel concentration and trajectory data sets (approximately 61,000, 14 × 14-km parcels). The simulations performed full surface and internal energy and mass balances within a multilayer snowpack evolution system. Processes and features accounted for included rainfall, snowfall, sublimation from static-surfaces and blowing-snow, snow melt, snow density evolution, snow temperature profiles, energy and mass transfers within the snowpack, superimposed ice, and ice dynamics. The simulations produced horizontal snow spatial structures that likely exist in the natural system but have not been revealed in previous studies spanning these spatial and temporal domains. Blowing-snow sublimation made a significant contribution to the snowpack mass budget. The superimposed ice layer was minimal and decreased over the last four decades. Snow carryover to the next accumulation season was minimal and sensitive to the melt-season atmospheric forcing (e.g., the average summer melt period was 3 weeks or 50% longer with ERA5 forcing than MERRA-2 forcing). Observed ice dynamics controlled the ice parcel age (in days), and ice age exerted a first-order control on snow property evolution., (©2020. The Authors.)

[1] The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument was launched in October 2011 as part of the Suomi National Polar-Orbiting Partnership (S-NPP). The VIIRS instrument was designed to improve upon the capabilities of the operational Advanced Very High Resolution Radiometer and provide observation continuity with NASA's Earth Observing System's Moderate Resolution Imaging Spectroradiometer (MODIS). Since the VIIRS first-light images were received in November 2011, NASA- and NOAA-funded scientists have been working to evaluate the instrument performance and generate land and cryosphere products to meet the needs of the NOAA operational users and the NASA science community. NOAA's focus has been on refining a suite of operational products known as Environmental Data Records (EDRs), which were developed according to project specifications under the National Polar-Orbiting Environmental Satellite System. The NASA S-NPP Science Team has focused on evaluating the EDRs for science use, developing and testing additional products to meet science data needs, and providing MODIS data product continuity. This paper presents to-date findings of the NASA Science Team's evaluation of the VIIRS land and cryosphere EDRs, specifically Surface Reflectance, Land Surface Temperature, Surface Albedo, Vegetation Indices, Surface Type, Active Fires, Snow Cover, Ice Surface Temperature, and Sea Ice Characterization. The study concludes that, for MODIS data product continuity and earth system science, an enhanced suite of land and cryosphere products and associated data system capabilities are needed beyond the EDRs currently available from the VIIRS.

Uncertainty in future water supplies for the Phoenix Metropolitan Area (Phoenix) are exacerbated by the near certainty of increased, future water demands; water demand may increase eightfold or more by 2030 for some communities. We developed a provider-based water management and planning model for Phoenix termed WaterSim 4.0. The model combines a FORTRAN library with Microsoft C# to simulate the spatial and temporal dynamics of current and projected future water supply and demand as influenced by population demographics, climatic uncertainty, and groundwater availability. This paper describes model development and rationale. Water providers receive surface water, groundwater, or both depending on their portfolio. Runoff from two riverine systems supplies surface water to Phoenix while three alluvial layers that underlie the area provide groundwater. Water demand was estimated using two approaches. One approach used residential density, population projections, water duties, and acreage. A second approach used per capita water consumption and separate population growth estimates. Simulated estimates of initial groundwater for each provider were obtained as outputs from the Arizona Department of Water Resources (ADWR) Salt River Valley groundwater flow model (GFM). We compared simulated estimates of water storage with empirical estimates for modeled reservoirs as a test of model performance. In simulations we modified runoff by 80%-110% of the historical estimates, in 5% intervals, to examine provider-specific responses to altered surface water availability for 33 large water providers over a 25-year period (2010-2035). Two metrics were used to differentiate their response: (1) we examined groundwater reliance (GWR; that proportion of a providers' portfolio dependent upon groundwater) from the runoff sensitivity analysis, and (2) we used 100% of the historical runoff simulations to examine the cumulative groundwater withdrawals for each provider. Four groups of water providers were identified, and discussed. Water portfolios most reliant on Colorado River water may be most sensitive to potential reductions in surface water supplies. Groundwater depletions were greatest for communities who were either 100% dependent upon groundwater (urban periphery), or nearly so, coupled with high water demand projections. On-going model development includes linking WaterSim 4.0 to the GFM in order to more precisely model provider-specific estimates of groundwater, and provider-based policy options that will enable "what-if" scenarios to examine policy trade-offs and long-term sustainability of water portfolios., (Published by Elsevier Ltd.)

The recommended dose (bolus 0.4 mg/kg followed by 0.15 mg/kg per hour) of lepirudin, a direct thrombin inhibitor licensed for treatment of heparin-induced thrombocytopenia (HIT), is too high. Starting in 2001, we omitted the bolus and reduced maintenance dose by at least one-third. Analyzing 53 HIT patients treated between January 2001 and February 2007, we observed that therapeutic anticoagulation intensity already 4 hours after lepirudin start had been reached with the following initial lepirudin doses (median): 0.078 mg/kg per hour [creatinine clearance (CrCl) more than 60 mL/min], 0.040 mg/kg per hour (CrCl 30-60 mL/min), and 0.013 mg/kg per hour (CrCl < 30 mL/min). The efficacy of this treatment was documented by increasing platelets and decreasing D-dimers. Based on this experience, we derived a lepirudin dosing regimen, which was prospectively evaluated treating 15 HIT patients between March 2007 and February 2008. We show that omitting the initial lepirudin bolus and administering 0.08 mg/kg per hour in patients with CrCl more than 60 mL/min, 0.04 mg/kg per hour in patients with CrCl 30-60 mL/min, and 0.01 to 0.02 mg/kg per hour in those with CrCl less than 30 mL/min is efficacious and safe, as documented by increasing platelet counts, decreasing D-dimer levels, and rare thrombotic (1 of 46) and major bleeding (4 of 46) complications.

Background: In the kidney, the trachea, and the colon, nitric oxide (NO) can modulate transepithelial fluid transport. This study investigates whether isolated human and porcine ciliary processes produce NO., Methods: Porcine ciliary processes and iris were used either fresh or thawed after storage at -70 degrees C. Post-mortem (8-12 h) human ciliary processes were used thawed after storage at -70 degrees C. NO was measured by placing a nafion-coated polymeric porphyrinic microsensor (differential pulse voltammetry) on the surface of the tissue. Measurements were conducted in the absence or in the presence of the NO formation inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 0.2 mM, 1 mM) or its biologically inactive D-enantiomer N(G)-nitro-D-arginine methyl ester (D-NAME; 1 mM)., Results: NO concentrations in porcine ciliary processes (1.27+/-0.25 microM) were higher (P=0.001) than those in the iris (0.00+/-0.02 microM) and were significantly (P<0.001) decreased by L-NAME (fresh specimen). From thawed porcine ciliary processes, NO concentrations measured (1.85+/-0.47 microM) were not significantly different (P=0.16) from those measured in fresh specimen and were also reduced (P <0.001) by L-NAME, but not by D-NAME. In human ciliary processes, NO concentrations measured (0.08+/-0.11 microM) were somehow lower but were again decreased (P<0.001) by L-NAME (thawed specimen)., Conclusion: Reflecting the biological activity of a nitric oxide synthase, isolated human and porcine ciliary processes produce NO.

Background: NO regulates vascular tone and structure, platelets, and monocytes. NO is synthesized by endothelial NO synthase (eNOS). Endothelial dysfunction occurs in atherosclerosis., Methods and Results: With a porphyrinic microsensor, NO release was measured in atherosclerotic human carotid arteries and normal mammary arteries obtained during surgery. eNOS protein expression was analyzed by immunohistochemistry. In normal arteries, the initial rate of NO release after stimulation with calcium ionophore A23187 (10 micromol/L) was 0.42+/-0.05 (micromol/L)/s (n=10). In contrast, the initial rate of NO release was markedly reduced in atherosclerotic segments, to 0.08+/-0.04 (micromol/L)/s (n=10, P<0.0001). NO peak concentration in normal arteries was 0.9+/-0.09 micromol/L (n=10) and in atherosclerotic segments, 0.1+/-0.03 micromol/L (n=10, P<0.0001). Reduced NO release in atherosclerotic segments was accompanied by marked reduction of immunoreactive eNOS in luminal endothelial cells, although specific endothelial cell markers (CD31) were present (n=13). Endothelial cells of vasa vasorum of atherosclerotic segments, however, remained positive for eNOS, as was the endothelium of normal arteries., Conclusions: In clinically relevant human atherosclerosis, eNOS protein expression and NO release are markedly reduced. This may be involved in the progression of atherosclerosis.

Atherosclerosis and its consequences account for most of the morbidity and mortality in Western countries. It is a disease of the intima and primarily involves four cell types, i.e., endothelial and vascular smooth muscle cells, monocytes and platelets. In recent years, knowledge on the cellular and molecular mechanisms of these cells and their alterations by cardiovascular risk factors and in atherosclerosis has greatly expanded. In particular, it has become clear that endothelial cells play a crucial role in the regulation of platelet function, coagulation, and vascular tone and structure. Interestingly, endothelial dysfunction occurs early, particularly if cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes are present. This could lead to adhesion of circulating platelets and monocytes and increased accumulation of lipids in the intima, as well as increased contraction, migration and proliferation of vascular smooth muscle cells. One of the enzymes with a key role in vascular homeostasis is angiotensin I converting enzyme (ACE). ACE is located on the endothelial cell membrane and is responsible for the conversion of angiotensin I into angiotensin II, as well as for the breakdown of bradykinin. While the antihypertensive effect of ACE inhibitors probably contributes to their antiatherogenic effects, other mechanisms are likely to be of greater importance. These direct antiatherogenic effects attributable to ACE inhibition are related to their vasculoprotective properties, including antiproliferative and antimitogenic activity, effects on endothelial function, protection against plaque rupture, antithrombotic effects, and possible antioxidant properties. There is overwhelming evidence to demonstrate the beneficial effects of long-term ACE inhibitor treatment in heart failure, acutely for suspected myocardial infarction (MI), and following MI in patients with left ventricular dysfunction. Hypercholesterolemia is a health risk, and epidemiological studies have shown a line between total cholesterol levels and the risk of cardiac events. Studies have shown that lowering the levels of total and low-density lipoprotein cholesterol using HMG-CoA reductase inhibitors can result in a decrease in cardiac morbidity and mortality. Angiographic studies of coronary arteries have demonstrated a disparity between the decrease in cardiac events and the extent of regression of coronary artery lesions. Mechanisms other than the regression of coronary stenosis may therefore be important in the beneficial effect of cholesterol lowering. It may be of major importance that lipid-lowering therapy is associated with improved endothelial function and decreased platelet activity. Thus, both ACE inhibitors and HMG-CoA reductase inhibitors have vasculoprotective properties which may explain their beneficial effects on cardiovascular morbidity and mortality.

The endothelium takes part in the regulation of vascular tone through the production of endothelium-derived relaxing and contracting factors. The L-arginine pathway within endothelial cells in the blood vessel wall is the source of production of the endogenous nitrovasodilator, nitric oxide (NO). The NO molecule has one unpaired electron and readily reacts with oxygen, superoxide radicals, or transition metals. Therefore the measurement of the concentration of NO in biological systems is a challenging analytical problem. NO is formed from L-arginine via constitutive NO synthase. It is released under basal conditions and in response to mechanical stimuli such as shear stress and in response to receptor-operated agonists such as bradykinin, serotonin, ADP/ATP, thrombin, histamine and substance P. NO is the mediator of endothelium-dependent relaxation in the circulation and exerts its effects by activating soluble guanylyl cyclase in vascular smooth muscle, which in turn leads to the formation of cyclic guanosine monophosphate (cyclic GMP) and to relaxation. In addition to its effect on vascular smooth muscle, NO is also released albuminally to interact with circulating platelets. Increases in cyclic GMP in platelets are associated with a decreased adhesion and aggregation. In endothelial cells, NO inhibits its own production as well as that of the vasoconstrictor peptide endothelin-1. Thus, endothelium-derived NO, through its vasodilator and anti-aggregatory properties, prevents vasospasm and thrombus formation in the circulation and thereby helps to maintain blood flow to vital organs such as the heart. Under certain conditions such as inflammation, NO may also be formed via inducible nitric oxide synthase by smooth muscle cells, endothelium and monocytes. Therapeutic nitrates also exert their effects by releasing NO from their molecules and activating soluble guanylyl cyclase. Their effects are particularly pronounced in arteries in which the release of NO is inhibited or impaired or in the absence of the endothelium. Thus, the endothelial L-arginine pathway plays an important protective role in the local regulation of blood flow and through its vasodilator and antiplatelet properties. Nitrates can at least in part substitute the endogenous nitrovasodilator in disease states with impaired formation of NO.

The efficacy of vasodilation depends on the drug and the contractile agonist involved. Furthermore, vasodilation also may be detrimental (i.e., coronary steal), possibly depending on the anatomic site and/or action of the vasodilator. We investigated the effects of Ca2+ antagonism in porcine epicardial and intramyocardial coronary arteries suspended in organ chambers filled with physiological salt solution (95% O2/5% CO2, 37 degrees C); isometric tension was measured. In epicardial vessels contracted with KCl, the thromboxane analogue U 46619, or endothelin-1 (ET-1), relaxations to the Ca2+ antagonist mibefradil were most effective after precontraction with KCl, followed by U 46619 and ET-1. In intramyocardial vessels, the contraction to KCl, U 46619, and particularly ET-1, was much more effectively inhibited by mibefradil than in epicardial arteries. In vessels preincubated with mibefradil, the drug was moderately effective in preventing the initiation of contractions. Preincubation with the inhibitor of nitric oxide production (NO), L omega-nitro arginine methyl ester (L-NAME) or endothelium removal, did not increase relaxations to mibefradil. However, epicardial but not intramyocardial vessels incubated with mibefradil exhibited enhanced relaxations to bradykinin (BK) and sodium nitroprusside (SNP) as compared with control. Thus, Ca2+ antagonism is particularly effective in intramyocardial coronary arteries. In addition to its inhibitory effects on contractility, calcium antagonism facilitates the effects of endothelium-derived NO in epicardial coronaries at the level of vascular smooth muscle (VSM).

Background: Endothelium-derived substances and the renin-angiotensin system are important regulators of vascular tone. This study was designed to evaluate the effects of age and hypertension on vascular function of rat coronary arteries., Methods and Results: Rings of the left anterior descending coronary artery were isolated from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 12 (younger) and 72 (older) weeks of age and suspended in myographs (37 degrees C, 95% O2/5% CO2) for isometric tension recording. Systolic blood pressure was higher in SHR than in WKY rats (P < .05) but was unaffected by age in both strains. Active wall tension to KCl 100 mmol/L (mN/mm) was decreased in younger (0.28 +/- 0.03, n = 9) and older SHR (0.49 +/- 0.06, n = 13) compared with age-matched WKY rats (0.87 +/- 0.05, n = 9 and 1.51 +/- 0.11, n = 11, respectively, P < .05). In both strains, active wall tension to endothelin-1 and serotonin increased with age (n = 6 to 10, P < .05) but was decreased in younger and older SHR compared with WKY rats (P < .05). Active wall tension induced by angiotensin I 10(-7) mol/L was increased in older SHR (0.19 +/- 0.04, n = 7) compared with younger SHR (0.04 +/- 0.01, n = 9) but was similar in younger and older WKY rats (0.10 +/- 0.02 versus 0.15 +/- 0.03, n = 6 to 9) and younger SHR. In younger WKY rats and SHR, pretreatment of coronary arteries with benazeprilat 10(-5) mol/L (n = 5 for each) almost completely abolished the contractions to angiotensin I 10(-7) mol/L. Active wall tension to angiotensin II 10(-7) mol/L was comparable in all four groups, but compared with the contraction to KCl 100 mmol/L, the response was already increased in younger SHR (29 +/- 3%, n = 9) compared with the younger WKY rats (14 +/- 3%, n = 9, P < .05), but it was unaffected by age in both strains. In vitro treatment of younger WKY rat and SHR coronary arteries with the nonpeptide angiotensin II (AT1) receptor antagonist valsartan 10(-5) mol/L (n = 3 for each) fully suppressed contractions to angiotensin II 10(-7) mol/L. In contrast, endothelium-independent relaxations to the nitrovasodilator sodium nitroprusside, endothelium-dependent relaxations to acetylcholine, and endothelium-dependent contractions to N omega-nitro-L-arginine methyl ester were comparable in all four groups of rats., Conclusions: In summary, in rat coronary arteries, contractile responses to endothelin-1, serotonin, and KCl increase with age but are decreased by hypertension. In contrast, the L-arginine/nitric oxide pathway remains unaffected. The contractions to angiotensin I markedly increased with increasing duration of hypertension in the SHR only. Despite overall reduced contractile responses of SHR coronary arteries, contractions to angiotensin II were maintained. Hence, aging and hypertension affect contractile responses of rat coronary arteries to vasoconstrictor agonists differently.

Endothelin-1 (ET-1) and angiotensin II (AII) are potent vasoconstrictor hormones which regulate tissue perfusion and blood pressure. We pharmacologically characterized endothelin and angiotensin receptors mediating contractions of human mammary resistance arteries in myographs for isometric tension recording. ET-1 caused potent contractions. The concentration response curve was shifted to the right by ETA antagonist FR 139317, but a high sensitivity, low efficacy component remained. After incubation with ETB agonist sarafotoxin (S6c) this component of the concentration response curve resistant to FR 139317 disappeared. The ETA/ETB-receptor antagonist bosentan shifted the entire concentration response curve to the right. AI and AII caused marked contractions. The effects of AI were reduced by the ACE inhibitor benazeprilat, while those of AII were prevented by valsartan, an AT1 antagonist. In summary, in human resistance arteries, contractions to ET-1 are mediated by ETA- and ETB-receptors while those to AII are exclusively mediated by AT1-receptors.

Neurohumoral changes influencing peripheral vascular resistance play a major role in congestive heart failure (CHF). We studied vascular function in 1-year-old cardiomyopathic syrian hamsters with pulmonary congestion and age-matched control hamsters. Aorta and mesenteric resistance arteries were suspended in organ chambers and myographs, respectively, for isometric tension recording. In aorta and mesenteric resistance arteries, contractile responses to norepinephrine (NE) were comparable in cardiomyopathic hamsters and controls. After inhibition of nitric oxide (NO) formation with nitro-L-arginine methylester (L-NAME), contractions to NE were enhanced in aorta of cardiomyopathic hamsters (p < 0.05); no effect was noted in controls or mesenteric resistance arteries. Low doses of endothelin-1 (ET-1 10(-10)-10(-9) M) caused stronger contractions in aorta of cardiomyopathic hamsters as compared with controls (p < 0.05). The sensitivity and maximal contraction to ET were more pronounced in mesenteric resistance arteries as compared with aorta in both cardiomyopathic and control hamsters (p < 0.05-0.001). In both aorta and mesenteric resistance arteries, acetylcholine (ACh 10(-9)-10(-5) M) induced concentration-dependent relaxation, which was prevented by L-NAME (p < 0.001). Maximal endothelium-dependent relaxation was more pronounced in aorta of cardiomyopathic hamsters (p < 0.05), but not different in mesenteric resistance arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

It has recently been shown that nitric oxide (NO) or a labile NO-releasing compound is produced in endothelial cells. In the present study we measured the NO-release from human vascular smooth muscle cells in culture. The cells released an average 2.2 x 10(-9) moles nitric oxide per 10(8) cells in ten minutes with a large variation between different cell lines and passages without stimulators. The NO-release was markedly reduced by the inhibitor of NO-formation NG-momomethyl-L-arginine (L-NMMA, 10(-5) M) to 3% of the control levels (p less than 0.02, n = 4), but unaffected by acetylcholine, bradykinin or endothelin -1, -2 or -3. In a microperfusion system the compound released from human vascular smooth muscle cells caused profound relaxation of isolated rat mesenteric resistance arteries. Thus, human vascular smooth muscle cells in culture produce and release biologically active NO from L-arginine.

The endothelium produces relaxing and contracting substances, among them nitric oxide and endothelin. The role of the endothelium was investigated in the regulation of vascular tone in isolated porcine ophthalmic arteries suspended in a myograph system for isometric tension recording. In quiescent arteries with endothelium, the inhibitor of nitric oxide formation from L-arginine, L-NG-monomethyl arginine (L-NMMA), evoked endothelium-dependent contractions which were reversed by L-, but not D-arginine. In arteries contracted with serotonin, bradykinin evoked potent endothelium-dependent relaxations; L-NMMA markedly reduced the sensitivity but not the maximal response. Acetylcholine caused relaxations in preparations with endothelium but contractions in those without endothelium; L-NMMA prevented the relaxations and unmasked the contractions. The relaxations to the nitrovasodilator SIN-1 were more pronounced in preparations without than with endothelium. In quiescent arteries, quick stretching evoked endothelium-dependent contractions which were prevented by indomethacin. Endothelin-1, serotonin, and norepinephrine evoked concentration-dependent contractions with pD2 values of 8.1 +/- 0.1, 6.9 +/- 0.1, and 5.9 +/- 0.1, respectively. Removal of the endothelium markedly augmented the contractions induced by serotonin but not endothelin and norepinephrine. Thus, the endothelium profoundly affects vascular tone of the porcine ophthalmic artery. Endothelium-derived nitric oxide is released both under basal conditions and after stimulation with acetylcholine and bradykinin. It may play an important protective role in the circulation against vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.

Serotonin has many and opposing effects in the cardiovascular system. The vascular endothelium importantly contributes as a modulator and mediator of the cardiovascular effects of serotonin. Endothelial cells contain the enzyme monoaminooxidase which inactivates serotonin. In addition, endothelial cells are a source of vasodilator substances such as endothelium-derived relaxing factor, the endogenous nitrovasodilator. Nitric oxide is continuously formed by the arterial endothelium to inhibit the effects of vasoconstrictor substances such as serotonin. Accordingly, removal of the endothelium enhances contractions induced by serotonin in most vascular preparations. In certain blood vessels, such as the porcine and canine coronary artery, serotonin stimulates the release of endothelium-derived nitric oxide. Endothelium-dependent relaxations to serotonin also occur in intramyocardial porcine coronary resistance arteries. In contrast to porcine and canine arteries, endothelium-dependent relaxations to serotonin have not been demonstrated in the human coronary and internal mammary artery. In the porcine coronary artery with regenerated endothelium and in that with atherosclerotic changes, the endothelium facilitates contractions to serotonin, suggesting that an endothelium-derived contracting factor is released. Since indomethacin prevents this endothelium-dependent facilitation of contractions to serotonin in atherosclerotic porcine coronary arteries, a cyclooxygenase product is likely involved. Similarly, in the aorta of spontaneously hypertensive rats, the endothelium facilitates the contractions to serotonin. Thus, the endothelium can importantly modulate the response to serotonin. While in normal arteries, the cells inhibit the vasoconstrictor effects of the monoamine, the endothelium facilitates its contractions in atherosclerotic and hypertensive blood vessels.