Progestin enhances vasoconstrictor responses in postmenopausal women receiving estrogen replacement therapy.

Clinical and experimental evidence suggests that the cardioprotective effect of estrogen replacement is due to effects both on scrum lipids and on blood vessels. Current practice includes the use of a progestin in combination with estrogen if the patient still has her uterus: however, little is known about the effects of combination therapy on vascular reactivity. We therefore studied the effects of estrogen alone and with added progestin on forearm vascular resistance at rest, during reactive hyperemia, and after cold pressor stimulation using plethysmography in six healthy, postmenopausal women. Measurements were made before therapy: after giving conjugated estrogen i.v.; followed by a daily oral dose of 0.625 mg for 21 days; and sequentially after the addition of 10 mg of medroxyprogesterone acetate (MPA) for 10 days. Mean blood pressure did not change significantly. After 21 days of estrogen therapy, forearm blood flow, resting vascular resistance, and resistance after cold pressor stimulation did not change significantly. However, after addition of MPA, resting forearm vascular resistance rose significantly from baseline: 25.7 ±â€Š2.7 U (SE) versus 38.3 ±â€Š2.5 (p = 0.004). In addition, forearm vascular resistance rose to a higher level after cold pressor stimulus during combination therapy (32.3 ±â€Š5.9 vs. 58.4 ±â€Š5.7; p = 0.0057) than after estrogen replacement alone (32.3 ±â€Š5.9 vs. 37.7 ±â€Š5.3; p = NS). We conclude that combination hormone replacement therapy results in higher resting vascular resistance and increased pressor responsiveness than does estrogen replacement therapy alone.

The effect of propofol on haemodynamics: cardiac output, venous return, mean systemic filling pressure, and vascular resistances.

BACKGROUND: Although arterial hypotension occurs frequently with propofol use in humans, its effects on intravascular volume and vascular capacitance are uncertain. We hypothesized that propofol decreases vascular capacitance and therefore decreases stressed volume. METHODS: Cardiac output (CO) was measured using Modelflow(®) in 17 adult subjects after upper abdominal surgery. Mean systemic filling pressure (MSFP) and vascular resistances were calculated using venous return curves constructed by measuring steady-state arterial and venous pressures and CO during inspiratory hold manoeuvres at increasing plateau pressures. Measurements were performed at three incremental levels of targeted blood propofol concentrations. RESULTS: Mean blood propofol concentrations for the three targeted levels were 3.0, 4.5, and 6.5 µg ml(-1). Mean arterial pressure, central venous pressure, MSFP, venous return pressure, Rv, systemic arterial resistance, and resistance of the systemic circulation decreased, stroke volume variation increased, and CO was not significantly different as propofol concentration increased. CONCLUSIONS: An increase in propofol concentration within the therapeutic range causes a decrease in vascular stressed volume without a change in CO. The absence of an effect of propofol on CO can be explained by the balance between the decrease in effective, or stressed, volume (as determined by MSFP), the decrease in resistance for venous return, and slightly improved heart function. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register: NTR2486.

Intrathecal fentanyl blockade of afferent neural feedback from skeletal muscle during exercise in heart failure patients: Influence on circulatory power and pulmonary vascular capacitance.

BACKGROUND: Secondary pulmonary hypertension is common in heart failure (HF) patients. We hypothesized that inhibition of feedback from locomotor muscle group III/IV neurons contributes to reduced pulmonary vascular pressures independent of changes in cardiac function during exercise in HF. METHODS: 9 HF patients (ages, 60 ± 2; EF, 26.7 ± 1.9%; New York Heart Association classes, I-III) and 9 age/gender matched controls (ages, 63 ± 2) completed five-minutes of constant-load cycling (65% Workloadpeak) with intrathecal fentanyl or placebo on randomized separate days. Mean arterial pressure (MAP), heart rate (HR), end-tidal partial pressure of CO2 (PETCO2), and oxygen consumption (VO2) were measured at rest and exercise. Non-invasive surrogates for cardiac power (circulatory power, CircP=VO2 × MAP), stroke volume (oxygen pulse, O2pulse=VO2/HR), and pulmonary arterial pressure (GXCAP=O2pulse × PETCO2) were calculated. RESULTS: At rest and end-exercise, differences between fentanyl versus placebo were not significant for CircP in HF or controls. Differences between fentanyl versus placebo for GXCAP were not significant at rest in HF or controls. At end-exercise, GXCAP was significantly higher with fentanyl versus placebo in HF (691 ± 59 versus 549 ± 38 mL/beat × mmHg), but not controls (536 ± 59 versus 474 ± 43 mL/beat × mmHg). Slopes (rest to end-exercise) for GXCAP were significantly higher with fentanyl versus placebo in HF (95.1 ± 9.8 versus 71.6 ± 6.0 mL/beat × mmHg), but not controls (74.3 ± 9.5 versus 60.8 ± 6.5 mL/beat × mmHg). CircP slopes did not differ between fentanyl versus placebo in HF or controls (p>0.05). CONCLUSION: We conclude that feedback from locomotor muscle group III/IV neurons may evoke increases in pulmonary vascular pressures independent of changes in cardiac function during exercise in HF.

Dual effects of resveratrol on arterial damage induced by insulin resistance in aged mice.

Aging leads to increased insulin resistance and arterial dysfunction, with oxidative stress playing an important role. This study explored the metabolic and arterial effects of a chronic treatment with resveratrol, an antioxidant polyphenol compound that has been shown to restore insulin sensitivity and decrease oxidative stress, in old mice with or without a high-protein diet renutrition care. High-protein diet tended to increase insulin resistance and atheromatous risk. Resveratrol improved insulin sensitivity in old mice fed standard diet by decreasing homeostasis model of assessment-insulin resistance and resistin levels. However, resveratrol did not improve insulin resistance status in old mice receiving the high-protein diet. In contrast, resveratrol exhibited deleterious effects by increasing inflammation state and superoxide production and diminishing aortic distensibility. In conclusion, we demonstrate that resveratrol has beneficial or deleterious effects on insulin sensitivity and arterial function, depending on nutritional status in our models.

Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels.

After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca(2+)-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca(2+)-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.

Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels

After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca2+-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca2+-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.(AU)

Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels

After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca2+-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca2+-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.

The role of endothelium in the vasorelaxant effects of the essential oil of Ocimum gratissimum in aorta and mesenteric vascular bed of rats.

This study investigated the endothelium-dependent vasorelaxant effects of the essential oil of Ocimum gratissimum (EOOG) in aortas and mesenteric vascular beds isolated from rats. EOOG (3-300 µg/mL) relaxed the tonic contractions induced by phenylephrine (0.1 µmol/L) in isolated aortas in a concentration-dependent manner in both endothelium-containing and endothelium-denuded preparations. This effect was partially reversed by L-NAME (100 µmol/L) but not by indomethacin (10 µmol/L) or TEA (5 mmol/L). In mesenteric vascular beds, bolus injections of EOOG (30, 50, 100, and 300 ng) decreased the perfusion pressure induced by noradrenaline (6 µmol/L) in endothelium-intact preparations but not in those treated with deoxycholate. L-NAME (300 µmol/L) but not TEA (1 mmol/L) or indomethacin (3 µmol/L) significantly reduced the vasodilatory response to EOOG at all of the doses tested. Our data showed that EOOG exerts a dose-dependent vasodilatory response in the resistance blood vessels of rat mesenteric vascular beds and in the capacitance blood vessel, the rat aorta. This action is completely dependent on endothelial nitric oxide (NO) release in the mesenteric vascular beds but only partially dependent on NO in the aorta. These novel effects of EOOG highlight interesting differences between resistance and capacitance blood vessels.

Adrenomedullin-epinephrine cotreatment enhances cardiac output and left ventricular function by energetically neutral mechanisms.

Adrenomedullin (AM) used therapeutically reduces mortality in the acute phase of experimental myocardial infarction. However, AM is potentially deleterious in acute heart failure as it is vasodilative and inotropically neutral. AM and epinephrine (EPI) are cosecreted from chromaffin cells, indicating a physiological interaction. We assessed the hemodynamic and energetic profile of AM-EPI cotreatment, exploring whether drug interaction improves cardiac function. Left ventricular (LV) mechanoenergetics were evaluated in 14 open-chest pigs using pressure-volume analysis and the pressure-volume area-myocardial O(2) consumption (PVA-MVo(2)) framework. AM (15 ng·kg(-1)·min(-1), n = 8) or saline (controls, n = 6) was infused for 120 min. Subsequently, a concurrent infusion of EPI (50 ng·kg(-1)·min(-1)) was added in both groups (AM-EPI vs. EPI). AM increased cardiac output (CO) and coronary blood flow by 20 ± 10% and 39 ± 14% (means ± SD, P < 0.05 vs. baseline), whereas controls were unaffected. AM-EPI increased CO and coronary blood flow by 55 ± 17% and 75 ± 16% (P < 0.05, AM-EPI interaction) compared with 13 ± 12% (P < 0.05 vs. baseline) and 18 ± 31% (P = not significant) with EPI. LV systolic capacitance decreased by -37 ± 22% and peak positive derivative of LV pressure (dP/dt(max)) increased by 32 ± 7% with AM-EPI (P < 0.05, AM-EPI interaction), whereas no significant effects were observed with EPI. Mean arterial pressure was maintained by AM-EPI and tended to decrease with EPI (+2 ± 13% vs. -11 ± 10%, P = not significant). PVA-MVo(2) relationships were unaffected by all treatments. In conclusion, AM-EPI cotreatment has an inodilator profile with CO and LV function augmented beyond individual drug effects and is not associated with relative increases in energetic cost. This can possibly take the inodilator treatment strategy beyond hemodynamic goals and exploit the cardioprotective effects of AM in acute heart failure.

Ascorbate improves circulation in postural tachycardia syndrome.

Low flow postural tachycardia syndrome (LFP) is associated with vasoconstriction, reduced cardiac output, increased plasma angiotensin II, reduced bioavailable nitric oxide (NO), and oxidative stress. We tested whether ascorbate would improve cutaneous NO and reduce vasoconstriction when delivered systemically. We used local cutaneous heating to 42°C and laser Doppler flowmetry to assess NO-dependent conductance (%CVC(max)) to sodium ascorbate and the systemic hemodynamic response to ascorbic acid in 11 LFP patients and in 8 control subjects (aged 23 ± 2 yr). We perfused intradermal microdialysis catheters with sodium ascorbate (10 mM) or Ringer solution. Predrug heat response was reduced in LFP, particularly the NO-dependent plateau phase (56 ± 6 vs. 88 ± 7%CVC(max)). Ascorbate increased baseline skin flow in LFP and control subjects and increased the LFP plateau response (82 ± 6 vs. 92 ± 6 control). Systemic infusion experiments used Finometer and ModelFlow to estimate relative cardiac index (CI) and forearm and calf venous occlusion plethysmography to estimate blood flows, peripheral arterial and venous resistances, and capacitance before and after infusing ascorbic acid. CI increased 40% after ascorbate as did peripheral flows. Peripheral resistances were increased (nearly double control) and decreased by nearly 50% after ascorbate. Calf capacitance and venous resistance were decreased compared with control but normalized with ascorbate. These data provide experimental support for the concept that oxidative stress and reduced NO possibly contribute to vasoconstriction and venoconstriction of LFP.

Limb-specific differences in the skin vascular responsiveness to adrenergic agonists.

In this study, to test the hypothesis that adrenergic vasoconstrictor responses of the legs are greater compared with the arms in human skin, cutaneous vascular conductance (CVC) in the forearm and calf were compared during the infusion of adrenergic agonists in healthy young volunteers. Under normothermic conditions, norepinephrine (NE, α- and ß-agonist, 1 × 10(-8) to 1 × 10(-2) M), phenylephrine (PHE, α(1)-agonist, 1 × 10(-8) to 1 × 10(-2) M), dexmedetomidine (DEX, α(2)-agonist, 1 × 10(-9) to 1 × 10(-4) M), and isoproterenol (ISO, ß-agonist, 1 × 10(-8) to 1 × 10(-3) M) were administered by intradermal microdialysis. Skin blood flow (SkBF) was measured by laser-Doppler flowmetry, and the local temperature at SkBF-measuring sites was maintained at 34°C throughout the experiments. CVC was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before drug infusion. The dose of NE at the onset of vasoconstriction and the effective dose (ED(50)) resulting in 50% of the maximal vasoconstrictor response for NE were lower (P < 0.001) in the calf than forearm. The ED(50) for PHE and DEX was also lower (P < 0.05) in the calf than forearm. Increases in CVC in response to ISO were potentially smaller in the calf, but the statistical differences in the responses were dependent on the expressions of CVC. These findings suggest that the cutaneous vasoconstrictor responsiveness to exogenous NE is greater in the legs than in the arms due to a higher α(1)- and α(2)-adrenoceptor reactivity, while the ß-adrenoceptor function plays a minor role in regional differences in adrenergic vasoconstriction in normothermic humans.

The physiologic implications of isolated alpha(1) adrenergic stimulation.

Phenylephrine and methoxamine are direct-acting, predominantly α(1) adrenergic receptor (AR) agonists. To better understand their physiologic effects, we screened 463 articles on the basis of PubMed searches of "methoxamine" and "phenylephrine" (limited to human, randomized studies published in English), as well as citations found therein. Relevant articles, as well as those discovered in the peer-review process, were incorporated into this review. Both methoxamine and phenylephrine increase cardiac afterload via several mechanisms, including increased vascular resistance, decreased vascular compliance, and disadvantageous alterations in the pressure waveforms produced by the pulsatile heart. Although pure α(1) agonists increase arterial blood pressure, neither animal nor human studies have ever shown pure α(1)-agonism to produce a favorable change in myocardial energetics because of the resultant increase in myocardial workload. Furthermore, the cost of increased blood pressure after pure α(1)-agonism is almost invariably decreased cardiac output, likely due to increases in venous resistance. The venous system contains α(1) ARs, and though stimulation of α(1) ARs decreases capacitance and may transiently increase venous return, this gain may be offset by changes in afterload, venous compliance, and venous resistance. Data on the effects of α(1) stimulation in the central nervous system show conflicting changes, while experimental animal data suggest that renal blood flow is reduced by α(1)-agonists, and both animal and human data suggest that gastrointestinal perfusion may be reduced by α(1) tone.

Alterations in sympathetic neuroeffector transmission to mesenteric arteries but not veins in DOCA-salt hypertension.

We studied hypertension-associated changes in prejunctional alpha(2) adrenergic receptor (alpha(2)-AR) function using amperometry to monitor in vitro norepinephrine (NE) measured as oxidation currents. Vasoconstriction was measured using video imaging. NE release was induced by electrical stimulation of sympathetic nerves associated with mesenteric arteries (MA) and veins (MV) of sham and DOCA-salt hypertensive rats. NE oxidation currents were larger in DOCA-salt compared to sham MA; there were no differences between currents in sham and DOCA-salt MV. Increases in NE oxidation currents followed a multi-exponential time course in sham MA. In DOCA-salt MA and sham and DOCA-salt MV, the time course was mono-exponential. Yohimbine (alpha(2)-AR antagonist, 1 microM), caused a mono-exponential increase in NE oxidation currents in sham and DOCA-salt MA. Yohimbine increased NE oxidation currents and constrictions more in sham compared to DOCA-salt MA and compared to MV. UK 14,304 (alpha(2)-AR agonist, 1.0 microM), reduced currents less in DOCA-salt MA and sham and DOCA-salt MV compared to sham MA. Prazosin (alpha(1)-AR antagonist, 0.1 microM) did not alter NE oxidation currents. Prazosin inhibited constrictions more in DOCA-salt compared to sham MA and almost completely blocked constrictions in sham and DOCA-salt MV. Prazosin-resistant constrictions in MA were blocked by the P2 receptor antagonist, PPADS (10 microM). Prejunctional alpha(2)-ARs modify NE concentrations near neuroeffector junctions in MA and MV. alpha(2)-AR function is most prominent in MA and is impaired in DOCA-salt MA but not MV. Purinergic transmission predominates in sham MA. NE is the dominant vasoconstrictor in DOCA-salt MA and sham and DOCA-salt MV.

Altered mesenteric venous capacitance and volume pooling in cirrhotic rats are mediated by nitric oxide.

In cirrhosis, despite augmented blood volume, effective circulating volume is decreased. This implies abnormal regulation of blood volume, i.e., venous pooling. Because gut veins are the main blood reservoir, we studied mesenteric venous capacitance and compliance in a rat model of cirrhosis. Cirrhosis was induced by bile duct ligation (4 wk). Controls were sham operated. Changes in first-order mesenteric vein diameters induced by drugs, hemorrhage, and stepwise increases in portal pressure (inflatable cuff) were directly observed by intravital microscopy. Effects of nitric oxide on responses to acute graded hemorrhage were studied by use of selective NO synthase (NOS) isoform inhibitors. Pressures were related to diameters to assess capacitance and compliance. Compared with controls, cirrhotic rats demonstrated increased mesenteric venous capacitance and decreased compliance. Norepinephrine induced venoconstriction but did not affect compliance. Prazosin markedly diminished compliance in controls but not cirrhotics. Conversely, the nonspecific NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) decreased compliance in cirrhotics, but not controls. Tetrodotoxin venodilated controls, venoconstricted cirrhotics, and markedly decreased compliance in both groups. When hemorrhaged, controls rapidly venoconstricted to compensate for initial hypotension, whereas cirrhotic rats remained hypotensive because venoconstriction was severely blunted. Pretreatment with l-NAME or the selective neuronal NOS inhibitors S-methyl-l-thiocitrulline and 7-nitroindazole normalized the homeostatic responses of cirrhotic rats, whereas the selective endothelial-constitutive NOS inhibitor N-iminoethyl-l-ornithine did not affect the response. In conclusion, mesenteric veins of cirrhotic rats showed enhanced capacitance, attenuated compensatory constrictive response to hemorrhage, and decreased compliance. The first two abnormalities were caused by neuronal NOS-derived nitric oxide.

Effects of gastric distension on the cardiovascular system in rainbow trout (Oncorhynchus mykiss).

When animals feed, blood flow to the gastrointestinal tract increases to ensure an adequate oxygen supply to the gastrointestinal tissue and an effective absorption of nutrients. In mammals, this increase depends on the chemical properties of the food, as well as, to some extent, on the mechanical distension of the stomach wall. By using an inflatable nitrile balloon positioned in the stomach, we investigated the cardiovascular responses to mechanical stretch of the stomach wall in rainbow trout (Oncorhynchus mykiss). Distension with a volume equivalent to a meal of 2% of the body mass increased dorsal aortic blood pressure by up to 29%, and central venous blood pressure increased transiently nearly fivefold. The increase in arterial pressure was mediated by an increased vascular resistance of both the systemic and the intestinal circulation. Cardiac output, heart rate, and stroke volume (SV) did not change, and only transient changes in gut blood flow were observed. The increase in arterial pressure was abolished by the alpha-adrenergic antagonist prazosin, indicating an active adrenergic vasoconstriction, whereas the venous pressor response could be the consequence of a passive increase in intraperitoneal pressure. Our results show that mechanical distension of the stomach causes an instantaneous increase in general vascular resistance, which may facilitate a redistribution of blood to the gastrointestinal tract when chemical stimuli from a meal induce vasodilation in the gut circulation. The normal postprandial increase in gut blood flow in teleosts is, therefore, most likely partly dependent on mechanical stimuli, as well as on chemical stimuli.

Effects of freshwater and saltwater adaptation and dietary salt on fluid compartments, blood pressure, and venous capacitance in trout.

Trout are of interest in defining the relationship between fluid and salt balance on cardiovascular function because they thrive in freshwater (FW; volume loading, salt depleting), saltwater (SW; volume depleting, salt loading), and FW while fed a high-salt diet (FW-HS; volume and salt loading). The effects of chronic (>2 wk) adaptation to these three protocols on blood volume (51Cr red cell space), extracellular fluid volume (99mTc-diethylene triaminepenta-acetic acid space), arterial (dorsal aortic; P(DA)) and venous (ductus Cuvier; Pven) blood pressure, mean circulatory filling pressure (zero-flow Pven), and vascular capacitance were examined in the present study on unanesthetized rainbow trout. Blood volume, extracellular fluid volume, P(DA), Pven, and mean circulatory filling pressure progressively increased in the order SW < FW < FW-HS. Vascular capacitance in SW fish appeared to be continuous with the capacitance curve of FW fish and reflect a passive volume-dependent unloading of the venous system of FW fish. Vascular capacitance curves for FW-HS fish were displaced upward and parallel to those of FW fish, indicative of an active increase in unstressed blood volume without any change in vascular compliance. These studies are the first in any vertebrate to measure the relationship between fluid compartments and cardiovascular function during independent manipulation of volume and salt balance, and they show that volume, but not salt, balance is the primary determinant of blood pressure in trout. They also present a new paradigm with which to investigate the relative contributions of water and salt balance in cardiovascular homeostasis.

Gingival blood flow in periodontitis patients before and after periodontal surgery assessed in smokers and non-smokers.

BACKGROUND: The aim of this study was to evaluate the gingival blood flow of smokers and non-smokers with periodontal disease before and after surgical periodontal treatment. METHODS: Nine smokers and six non-smokers with at least two periodontal lesions were included in the study. Laser Doppler flowmetry was used to measure blood flow in two gingival sites and two skin sites. Two intrabony defects were treated surgically at the same time; enamel matrix derivative was applied at random to one of the sites, whereas the other site received a placebo gel. We measured resting gingival blood flow (GBF) and responses to cold pressor test (CPT) and to smoking and made continuous measurements of blood pressure (BP). Resting GBF levels of 26 young healthy subjects were used as a reference value. RESULTS: Resting GBF was significantly lower for the periodontitis patients compared to the reference subjects, regardless of smoking habits. GBF and gingival vascular conductance (VC) decreased significantly pre- and postoperatively in response to smoking. CPT evoked significant decreases in VC in smokers and non-smokers. Skin blood flow decreased significantly in response to CPT, more so in the non-smokers. BP was significantly higher in the non-smokers. CONCLUSIONS: Resting GBF of periodontitis patients was not lower in smokers than in non-smokers, but it was significantly lower than in the younger reference subjects. In contrast to our earlier findings in healthy subjects, smoking one cigarette may cause a decrease in GBF and VC in periodontitis patients. These observations suggested the existence of a dysfunction in the gingival vasculature in smokers and non-smokers with periodontitis.

Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat.

Somatosympathetic reflexes were studied in young hyperinsulinemic, insulin-resistant (Zucker fatty) rats (ZFR) and a related control (Zucker lean) strain (ZLR). Glucose metabolism was characterized by minimal model analysis of intravenous glucose tolerance test data. Seven-week-old ZFR (n=18) and ZLR (n=17) were studied under pentobarbital anesthesia. Mean body weight and plasma glucose and insulin concentration were significantly greater (P<0.05) in ZFR than in ZLR, whereas basal values of mean arterial pressure (MAP) and heart rate (HR) were not significantly different. Increments of MAP (DeltaMAP) and HR (DeltaHR) elicited by electrical stimulation of the sciatic nerve (5-s trains of 100 pulses, 0.5-ms pulse duration, 100- to 400-microA pulse intensity) were significantly higher (ANOVA, P<0.05) in ZFR at each level of stimulus intensity. Regression analysis showed a linear increase in DeltaMAP and DeltaHR with increasing sciatic nerve stimulus intensity. Pressor responses to phenylephrine after ganglionic blockade demonstrated that vascular reactivity to adrenergic stimulation is not increased in ZFR compared with ZLR. Thus this factor does not contribute to enhancement of somatosympathetic reflexes observed in this strain. Insulin sensitivity in ZFR was one-fourth (P<0.05) that in ZLR. These results suggest that stronger sympathetic nervous reactivity in ZFR is associated with a severe insulin-resistant state before the onset of hypertension and support the hypothesis that insulin-mediated stimulation of the sympathetic nervous system is involved in the development of cardiovascular diseases related to alterations of glucose metabolism.

Adrenergic control of venous capacitance during moderate hypoxia in the rainbow trout (Oncorhynchus mykiss): role of neural and circulating catecholamines.

Central venous blood pressure (P(ven)) increases in response to hypoxia in rainbow trout (Oncorhynchus mykiss), but details on the control mechanisms of the venous vasculature during hypoxia have not been studied in fish. Basic cardiovascular variables including P(ven), dorsal aortic blood pressure, cardiac output, and heart rate were monitored in vivo during normoxia and moderate hypoxia (P(W)O(2) = approximately 9 kPa), where P(W)O(2) is water oxygen partial pressure. Venous capacitance curves for normoxia and hypoxia were constructed at 80-100, 90-110, and 100-120% of total blood volume by transiently (8 s) occluding the ventral aorta and measure P(ven) during circulatory arrest to estimate the mean circulatory filling pressure (MCFP). This allowed for estimates of hypoxia-induced changes in unstressed blood volume (USBV) and venous compliance. MCFP increased due to a decreased USBV at all blood volumes during hypoxia. These venous responses were blocked by alpha-adrenoceptor blockade with prazosin (1 mg/kg body mass). MCFP still increased during hypoxia after pretreatment with the adrenergic nerve-blocking agent bretylium (10 mg/kg body mass), but the decrease in USBV only persisted at 80-100% blood volume, whereas vascular capacitance decreased significantly at 90-110% blood volume. In all treatments, hypoxia typically reduced heart rate while cardiac output was maintained through a compensatory increase in stroke volume. Despite the markedly reduced response in venous capacitance after adrenergic blockade, P(ven) always increased in response to hypoxia. This study reveals that venous capacitance in rainbow trout is actively modulated in response to hypoxia by an alpha-adrenergic mechanism with both humoral and neural components.

Effects of intravenous prostaglandin E1 on arterial compliance: a randomized controlled trial.

BACKGROUND: Prostanoids are in widespread use for the treatment of critical limb ischemia and are suggested to improve arterial compliance. However, dose- and time-dependency of these drug effects are indeterminate. We investigated the influence of intravenous application of prostanoids on arterial compliance parameters in patients with critical limb ischemia due to peripheral artery disease (PAD). PATIENTS AND METHODS: We included 82 consecutive patients with PAD Fontaine stage III and IV in a patient-blinded, randomized controlled trial. Patients were randomly assigned to either single dose intravenous treatment with 40 microg (n = 29) or 60 microg (n = 27) of Alprostadil (PGE1) in 250 ml 0.9% saline over 2 hours, or 250 ml 0.9% saline solution as a placebo group (n = 26). Large and small artery compliance was measured by peripheral pulse contour analysis at baseline, at one hour during intravenous infusion of Alprostadil, immediately after and 24 hours after the end of the infusion. For study purposes the patients received Alprostadil only once during the observation period of 2 days. RESULTS: Large artery compliance, blood pressure, heart rate and cardiac output were unaffected by PGE1 administration irrespectively of drug-dosage or time interval. Small artery compliance increased at 1 hour during intravenous application of Alprostadil (40 microg Alprostadil p = 0.001; 60 microg Alprostadil p < 0.0001) compared to placebo and increased median +47% (IQR +5% to +100%) after administration of 40 microg Alprostadil and median +32% (IQR -11% to +88%) after 60 microg Alprostadil (p = 0.5). Immediately after the end of Alprostadil infusion small artery compliance decreased to baseline levels. CONCLUSIONS: Prostaglandin E1 causes a significant improvement of small artery compliance during the time of intravenous application. However, this effect rapidly diminishes after the end of administration and no dose-dependency between 40 microg and 60 microg Alprostadil is observed.