Skeletal Muscle Vascular Resistance Research Articles

Muscular blood flow response to submaximal leg exercise in normal subjects and in patients with heart failure.

Blood flow to working skeletal muscle is usually reduced during exercise in patients with congestive heart failure. An intrinsic impairment of skeletal muscle vasodilatory capacity has been suspected as a mechanism of this muscle underperfusion during maximal exercise, but its role during submaximal exercise remains unclear. Therefore, we studied by transcutaneous Doppler ultrasonography the arterial blood flow in the common femoral artery at rest and during a submaximal bicycle exercise in 12 normal subjects and in 30 patients with heart failure. Leg blood flow was lower in patients than in control subjects at rest [0.29 +/- 0.14 (SD) vs. 0.45 +/- 0.14 l/min, P < 0.01], at absolute powers and at the same relative power (2.17 +/- 1.06 vs. 4.39 +/- 1.4 l/min, P < 0.001). Because mean arterial pressure was maintained, leg vascular resistance was higher in patients than in control subjects at rest (407 +/- 187 vs. 247 +/- 71 mmHg.l-1.min, P < 0.01) and at the same relative power (73 +/- 49 vs. 31 +/- 13 mmHg.l-1.min, P < 0.01) but not at absolute powers. Although the magnitude of increase in leg blood flow corrected for power was similar in both groups (31 +/- 10 vs. 34 +/- 10 ml.min-1.W-1), the magnitude of decrease of leg vascular resistance corrected for power was higher in patients than in control subjects (5.9 +/- 3.3 vs. 1.9 +/- 0.94 mmHg.l-1.min.W-1, P < 0.001). These results suggest that the ability of skeletal muscle vascular resistance to decrease is not impaired and that intrinsic vascular abnormalities do not limit vasodilator response to submaximal exercise in patients with heart failure.

Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs.

1. The distribution of cardiac output during administration of levosimendan, a new myofilament calcium sensitizer, is unknown. We examined and compared the effects of levosimendan, pimobendan, and milrinone on regional tissue perfusion by use of the radioactive microsphere technique in barbiturate-anaesthetized dogs. 2. Haemodynamics and regional blood flow were determined before and during infusions of levosimendan (0.75, 1.5, and 3.0 micrograms kg-1 min-1), pimobendan (10, 20, and 40 micrograms kg-1 min-1), or milrinone (1.0, 2.0, and 4.0 micrograms kg-1 min-1). 3. All three drugs caused similar increases in heart rate, cardiac output, and left ventricular +dP/dt and decreases in end-diastolic pressure and systemic vascular resistance. No changes in subendocardial, midmyocardial, and subepicardial blood flow occurred during administration of levosimendan. However, a redistribution of blood flow from subendocardium to subepicardium was observed. Pimobendan increased midmyocardial and subepicardial blood flow and reduced the endo/epi ratio to a greater degree than levosimendan. Milrinone did not affect myocardial perfusion. 4. Levosimendan increased blood flow to the renal medulla and decreased renal medullary and cortical vascular resistance. Levosimendan increased blood flow to the small intestine and liver and reduced vascular resistance in these organs. Pimobendan increased hepatic blood flow to a greater degree than levosimendan but did not alter small intestinal perfusion. All three drugs decreased splenic blood flow to similar degrees. Levosimendan and pimobendan reduced cerebral vascular resistance. Levosimendan and milrinone reduced skeletal muscle vascular resistance. 5. The results indicate that levosimendan, pimobendan, and milrinone cause subtlety different alterations in regional tissue perfusion while producing similar haemodynamic effects.

Vascular Actions of Insulin in Health and Disease

Insulin has well known metabolic effects. However, depending on the magnitude and duration of the insulin stimulus, this hormone can also produce vasodilation and vascular smooth muscle growth. The association of hyperinsulinemia with the metabolic disorders of obesity and non-insulin-dependent diabetes, as well as with the cardiovascular pathologies of hypertension and atherosclerosis, has led to suggestions that perhaps elevated insulin levels are causally related to these diseases. Alternatively, insulin resistance may develop following an increase in skeletal muscle vascular resistance, with or without hypertension, such that a reduction in skeletal muscle blood flow leads to an attenuated glucose delivery and uptake. These hypotheses are explored in this review by examining the effects of insulin on vascular smooth muscle tissue during both acute and prolonged exposure. An interaction among hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with the insulin resistant state is described whereby insulin resistance can be both a cause and a result of elevated vascular resistance. The association between blood flow and insulin stimulated glucose uptake suggests that therapeutic intervention against the development of skeletal muscle vascular resistance should occur early in individuals generally predisposed to cardiovascular pathology in order to attenuate, or avoid, insulin resistance and its sequelae.

Skeletal muscle vascular responses in human limbs to isometric handgrip

Studies of whole limb blood flow have shown that static handgrip elicits a vasodilatation in the resting forearm and vasoconstriction in the resting leg. We asked if these responses occur in the skeletal muscle vascular bed, and if so, what is the relative contribution of local metabolic versus other mechanisms to these vascular responses. Blood flow recordings were made simultaneously in the skeletal muscle of the resting arm and leg using the Xenon-washout method in ten subjects during 3 min of isometric handgrip at 30% of maximal voluntary contraction. In the arm, skeletal muscle vascular resistance (SMVR) decreased transiently at the onset of exercise followed by a return to baseline levels at the end of exercise. In the leg SMVR remained unchanged during the 1st min of handgrip, but had increased to exceed baseline levels by the end of exercise. During exercise electromyography (EMG) recordings from nonexercising limbs demonstrated a progressive 20-fold increase in activity in the arm, but remained at baseline in the leg. During EMG-signal modelled exercise performed to mimic the inadvertent muscle activity, decreases in forearm SMVR amounted to 57% of the decrease seen with controlateral handgrip. The present study would seem to indicate that vascular tone in nonexercising skeletal muscle in the arm and leg are controlled differently during the early stages of static handgrip. Metabolic vasodilation due to involuntary contraction could significantly modulate forearm skeletal muscle vascular responses, but other factors, most likely neural vasodilator mechanisms, must make major contributions. During the later stages of contralateral sustained handgrip, vascular adjustments in resting forearm skeletal muscle would seem to be the final result of reflex sympathetic vasoconstrictor drive, local metabolic vasodilator forces and possibly neurogenic vasodilator mechanisms.

Insulin differentially regulates systemic and skeletal muscle vascular resistance.

To explore the relationships among insulin action, vascular resistance, and insulin sensitivity, we studied three groups of lean (Ln) and one group of obese (Ob) men. Glucose uptake was measured in whole body (WBGU) and in leg muscle (LGU) under basal and hyperinsulinemic euglycemic conditions. Mean arterial pressure (MAP), cardiac output (CO), leg blood flow (LBF), and systemic (SVR) and leg (LVR) vascular resistance were also ascertained. Ln groups were studied during insulin infusion rates of 20, 40, and 600 mU.m-2.min-1 and the Ob group at 40 mU.m-2.min-1. In Ob vs. Ln groups, WBGU and LGU were reduced by 51 (P < 0.01) and 42% (P < 0.05), respectively. In response to insulin, LBF increased > 60% (P < 0.01) in Ln groups but only approximately 20% in the Ob group, P = not significant (NS). CO was unchanged in Ob compared with a 15% increase (P < 0.05) in Ln groups, LBF was highly correlated with CO, r 0.70, P < 0.001. During hyperinsulinemia, MAP and LVR decreased in Ln (P < 0.001) but not in the Ob group (P = NS). In Ln groups, SVR decreased by 26 vs. 9% in the Ob group, P < 0.01. In summary, 1) insulin decreases LVR more than SVR and via this mechanism redistributes CO to insulin-sensitive tissues, 2) this insulin effect is blunted in Ob humans, and 3) insulin decreases MAP and vascular resistance more effectively in insulin-sensitive than in insulin-resistant subjects. In conclusion, insulin resistance to carbohydrate metabolism is associated with resistance to insulin's effect to decrease skeletal muscle vascular resistance and as such could act as a risk factor for the development of hypertension.

Age-related alterations in the arterial microvasculature of skeletal muscle.

This study investigated the possibility that the aging process results in alterations in the structure and/or functional reactivity of the microvessels that could contribute to increased resistance to blood flow in working skeletal muscle. Initially, latex casts were made of the cremaster muscle microvasculature in adult (12 mo) and senescent (24 mo) male Fischer 344 rats. Although the average diameter was not different between age groups, segmental length (distance between adjacent branches) increased significantly (3rd order) during aging. Additionally, in vivo experiments were performed to determine the response of the vessels to the topical application of norepinephrine and adenosine. There was no increase in vasoconstriction produced by norepinephrine; however, the vasodilation in response to adenosine declined dramatically (1st and 2nd order) with advancing age. It can be concluded that the increase in skeletal muscle vascular resistance during contraction in aged male rats could be explained by morphological changes and/or the diminished vasodilation elicited by adenosine.

Effects of dopexamine hydrochloride, a beta‐adrenergic and dopaminergic agonist, on vascular resistances, and flow distribution between cutaneous and skeletal muscle vasculatures

AbstractLocal i.a. infusions of the dopaminergic and β2 adrenoceptor agonist dopexamine HCL (DPX) into collateral‐free, innervated canine forelimbs perfused at constant flow produced dose‐dependent decreases in perfusion pressure, evidence of a vasodilator response in the forelimb vasculature. DPX produced vasodilation in both the skin (cutaneous) and skeletal muscle vasculature of the canine forelimb, as evidenced by the dose‐dependent decrease in total skin and total skeletal muscle vascular resistances. DPX produced comparable dilation of the skin and skeletal muscle vasculatures, as evidenced by the failure of this agent to produce a significant shift in blood flow between the brachial and cephalic venous outflows, that is, between the skin and skeletal muscle vasculatures. In the cutaneous (skin) vascular circuit, DPX failed to affect vascular resistances in the large artery and large vein segments, but produced a dose‐dependent decrease in vascular resistance in the small vessel segment, presumably reflecting primarily arteriolar vasodilation. The vascular smooth muscle relaxation produced by DPX was inhibited by treatment with propranolol, suggesting that the vasodilation primarily results from direct stimulation of forelimb vascular β2 adrenoceptors by DPX.

Vascular effects, formation, clearance and release of endothelin peptides in the pig

The formation, release, clearance and vascular effects of endothelin (ET)-like immunoreactivity (-LI) was studied in the pig in vivo. Intravenous infusion of ET-1, 2 and 3 (20 pmol/kg/min for 20 min) increased vascular resistance in the kidney, spleen and skeletal muscle. The most pronounced effects were evoked by ET-1 which caused increases in renal, splenic and skeletal muscle vascular resistance of 554, 528 and 38%, respectively, and a threshold response was observed at 80 pmol/l ET-LI in arterial plasma. During the infusion a large portion of arterial plasma, ET-LI was cleared over the kidney, spleen and skeletal muscle, whereby the most pronounced clearance was observed for ET-1 (73-93%). The ET-1 precursor Big-ET (1-39) given in a similar dose produced only a slight increase in renal vascular resistance (by 20%) and was cleared only over the kidney and not over the spleen or skeletal muscle. Using an ET-1 specific antiserum it was found that plasma ET-1 levels increased 11-fold during the infusion of Big-ET, indicating formation of ET-1 from Big-ET. The half-lives of circulating ET-1, 2 and 3 were 1.3-2.1 min and of Big-ET 8.9 min. Induction of asphyxia for 2 min increased the overflow of ET-LI from the spleen, suggesting local release, and caused splenic vasoconstriction. During i.v. administration of endotoxin for 4 h, arterial plasma ET-LI increased 7-fold and renal and splenic vasoconstrictor responses developed that correlated significantly with the arterial plasma ET-LI. Furthermore, a local release of ET-LI in the spleen was observed during endotoxin administration. Chromatographic characterization of the ET-LI in plasma during endotoxin administration revealed presence of ET-1 and Big-ET. It is concluded that there exists specificity both concerning the vasoconstrictor effects and removal from the circulation of ET peptides, both mechanisms being most prominent for ET-1 in the kidney. Furthermore ET-1 seems to be formed from circulating Big-ET and release of ET-LI can be detected during situations like asphyxia and sepsis.

Combined effects of autoregulation and vasoconstrictors on hindquarters vascular resistance

Relative contributions of local autoregulatory tone and vasoconstrictor tone to skeletal muscle vascular resistance were studied in anesthetized rats during hypertension produced by vasoconstrictor infusion. Rats were instrumented with a Doppler flow probe on the sacral aorta (SA) to measure blood flow and to allow calculation of vascular resistance. An occluder was placed on the SA and used to produce stepwise reductions in local perfusion pressure. Pressure-flow curves for the hindquarters were obtained in the absence and presence of elevated mean arterial pressure (MAP) produced by infusion of angiotensin II (ANG II; 50-1,247 ng.kg-1.min-1) or phenylephrine (PE; 2.5-12.4 micrograms.kg-1.min-1). Both ANG II and PE infusion increased MAP. For example, MAP was increased by ANG II from 91 to 134 mmHg and by PE from 89 to 156 mmHg. In addition, infusions of ANG II and PE produced dose-dependent rightward shifts in the hindquarters pressure-flow relationship. To examine the effect of pressure on the dose-response relationships of ANG II or PE, local perfusion pressure was adjusted to remain constant at various pressure levels that were independent of MAP during drug infusions. This produced a series of distinct dose-response curves with each curve defined by a different pressure level and with each characterized by a different maximum change in vascular resistance. If local perfusion pressure was not held constant but was permitted to increase with MAP, a compound dose-response curve was obtained in which the combined effects of the change in local pressure (i.e., autoregulation) and vasoconstrictor dose on vascular resistance could be discerned. These data demonstrate that hindquarters blood flow autoregulation continues to occur in the presence of vasoconstrictors. Consequently, autoregulatory mechanisms may be stimulated by any increase in MAP whether associated with systemic vasoconstrictor infusion or activation of neurohumoral pressor systems. The result is an amplified rise in local vascular resistance.

Ischemia-reperfusion injury in isolated rat hindquarters

The purpose of this study was to determine the suitability of the maximally vasodilated (papaverine) isolated rat hindquarters preparation to study the effects of ischemia and reperfusion on the microvasculature of skeletal muscle. The osmotic reflection coefficient for plasma proteins (sigma) and total vascular resistance (RT, mmHg.ml-1.min.100 g-1) were determined before ischemic periods of 30, 60, 120, 180, and 240 min in intact (with skin) and 30, 60, and 120 min in skinned hindquarters and again after 60 min of reperfusion. In both intact and skinned hindquarters, reductions in sigma and increases in RT were observed during reperfusion and were correlated with the ischemic period duration. After 120 min of ischemia in intact and skinned hindquarters, sigma was reduced from preischemia values of 0.92 +/- 0.02 and 0.89 +/- 0.02 to 0.61 +/- 0.03 and 0.57 +/- 0.03, respectively, whereas RT was increased from preischemia levels of 8.9 +/- 0.3 and 8.1 +/- 0.1 to 28.4 +/- 2.9 and 74.2 +/- 16.8, respectively. The increases in RT were associated with proportional increases in skeletal muscle vascular resistance. Thus, in isolated rat hindquarters, increasing the duration of ischemia results in progressive increases in the permeability to plasma proteins (decreased sigma) and RT, which are associated primarily with skeletal muscle.

A study of the effect of isoflurane anaesthesia on equine skeletal muscle perfusion.

The effects of 1.1, 1.5 and 1.8 MAC (minimum alveolar concentration) isoflurane-02 anaesthesia on skeletal muscle blood flow, 02 delivery and vascular resistance were studied in the non-dependent region of seven healthy normothermic, isocapnoeic ponies. Muscle blood flow was determined with 15 microns diameter radionuclide labelled microspheres that were injected into the left ventricle. Muscle blood flow during anaesthesia was compared to unanaesthetised (control) measurements. Isoflurane administration caused a dose dependent decrease in mean aortic pressure, and skeletal muscle (temporalis, triceps brachii, longissimus dorsi, gluteus medius, biceps femoris, vastus lateralis) blood flow. However, in the masseter, triceps brachii at 1.1 and 1.5 MAC, and longissimus dorsi lumborum at 1.1 MAC anaesthesia, blood flow values were not different from the control value. Vascular resistance did not change significantly in any of the muscles with any concentration of isoflurane. With the exception of the masseter muscle, isoflurane anaesthesia also decreased skeletal muscle 02 delivery. There were no significant differences in the muscle parameters studied between the three concentrations of isoflurane. Because skeletal muscle vascular resistance was unchanged throughout the study, it is possible that there may be an interference of 'autoregulation' in the skeletal muscle vascular beds of isocapnoeic ponies during isoflurane-02 anaesthesia.

Naloxone does not affect muscle blood flow during low intensity exercise in rats.

The purpose of this study was to determine whether endogenous opioids are involved in the control of skeletal muscle blood flow during locomotory exercise in rats. The radiolabeled miscrosphere technique was used to measure total and regional muscle blood flow. We first determined whether methionine enkephalin (1,000 micrograms.kg-1 I.V.) would produce vasodilation in muscle vascular beds. We found that methionine enkephalin produced a 36 mm Hg (range of 20-50 mm Hg) drop in mean arterial pressure (Pa), which was associated with decreases in calculated skeletal muscle vascular resistance in anesthetized rats, and that these effects on arterial pressure and skeletal muscle vascular resistance were blocked by the infusion of naloxone (10 micrograms.kg-1). Measurements were then made at 5 min of treadmill exercise at 15 m.min-1 (0 degree incline) and following exercise in both saline-treated (controls) and naloxone (10 micrograms.kg-1)-treated conscious rats. There were no differences between the heart rates, blood pressures, or total muscle blood flows of the two groups. There were also no significant differences between the blood flows to 32 hind limb muscle samples composed of various muscle fiber types. Since naloxone blockade did not affect total or regional muscle blood flow during low intensity exercise, it appears that the endogenous opioids are not required for the normal exercise hyperemia of skeletal muscles.

Neuropeptide Y and control of vascular resistance in skeletal muscle

The effect of neuropeptide Y (NPY) on the increase in skeletal muscle vascular resistance caused by exogenous noradrenaline and by sympathetic stimulation was examined in gracilis muscles of anaesthetised dogs. NPY potentiated the increases in resistance caused by both of these to similar degrees. Although NPY itself often caused an elevation in the basal resistance, correlation coefficients for the percentage increase in basal resistance due to NPY and the percentage increase in the evoked sympathetic and noradrenergic responses in the presence of NPY indicated that it was the NPY itself (rather than the increase in basal resistance per se) which was responsible for the potentiation. The potentiation was apparently biphasic, with an initial peak in response during the first 20 min following administration of NPY followed by a secondary peak between 30 and 60 min. Radioimmunoassay for plasma levels of NPY indicated that the secondary increase of vascular resistance was not associated with a secondary peak in the plasma level of NPY.

Neurogenic histaminergic vasodilation in canine skeletal muscle: mediation by alpha 2-adrenoceptor stimulation.

This study examines the neurogenic effect of alpha 2-adrenoceptor stimulation on skeletal muscle vascular resistance and its relation to the level of background sympathetic activity. The isolated, separately perfused, neurally intact canine gracilis muscle preparation was used since it permits deliberate and quantifiable alterations in background sympathetic activity, as measured by skeletal muscle vascular resistance. Systemic intravenous UK-14304, a highly selective alpha 2-adrenoceptor agonist, produced a precipitous, neurogenic vasodilation that lowered vascular resistance below the subsequently denervated resistance, thus indicating that an active vasodilation was involved. The overall magnitude of the vasodilation was much greater in animals that had been hemorrhaged to elevate background sympathetic activity than in animals that had been transfused to lower background activity. The neurogenic vasodilation was unaffected by baroreceptor and cardiopulmonary receptor denervation and by prior cholinergic-receptor blockade of the gracilis muscle. Prior H1- and H2-histaminergic-receptor blockade, on the other hand, eliminated the active vasodilation but not a vasodilation down to the subsequently denervated resistance. Prior alpha 1-adrenoceptor blockade lowered resistance down to the subsequently denervated resistance and greatly attenuated the active vasodilation. The present study demonstrates that withdrawal of sympathetic activity by alpha 2-adrenoceptor stimulation produces an active vasodilation resulting from histamine release in skeletal muscle as well as a passive vasodilation resulting from lysis of peripheral vasoconstrictor tone.

Vascular injury in dogs during ischemia-reperfusion: improvement with ATP-MgCl2 pretreatment.

The aim of this study was to determine whether ATP-MgCl2 or isoproterenol pretreatment would attenuate the increase in canine gracilis muscle vascular resistance and permeability associated with 4 h of occlusive ischemia followed by 1 h of reperfusion. To this end, the osmotic reflection coefficient for total plasma proteins (omega), isogravimetric capillary pressure (Pci), precapillary resistance (Ra), postcapillary resistance (Rv), and total vascular resistance (Rt) were determined for the following conditions: control, ischemia, and ischemia plus pretreatment with ATP-MgCl2 or isoproterenol. Reperfusion, after ischemia, significantly reduced omega from 0.94 +/- 0.02 to 0.64 +/- 0.02, whereas Pci was decreased by 50 +/- 4%, indicating a dramatic increase in vascular permeability. Ischemia-reperfusion was also associated with an increase in Rt of 230 +/- 22%. Similar results were obtained in muscles pretreated with isoproterenol. However, in muscles pretreated with ATP-MgCl2, omega averaged 0.98 +/- 0.09, Pci was reduced by only 15 +/- 8%, and Rt was increased by just 25 +/- 12%. The effect of ATP-MgCl2 on neutrophilic oxidative metabolism was evaluated by measuring superoxide production by activated neutrophils in the presence and absence of ATP-MgCl2. Superoxide production by activated neutrophils was significantly attenuated by ATP-MgCl2. The results of these studies indicate that pretreatment with ATP-MgCl2, but not isoproterenol, is remarkably effective in attenuating the increase in skeletal muscle vascular resistance and permeability induced by ischemia-reperfusion. The protective effect of ATP-MgCl2 may be related in part to its ability to inhibit neutrophilic superoxide production.

Effects of the Novel Calcium Channel Blocker, McN-5691, on Cardiocirculatory Dynamics and Cardiac Output Distribution in Conscious Spontaneously Hypertensive Rat

The purpose of this study was to characterize the cardiocirculatory effects of McN-5691 in the conscious spontaneously hypertensive rat (SHR) and in age matched Wistar-Kyoto (WKY) control rats. Animals were instrumented under halothane anesthesia for right atrial, left ventricular arterial, and venous pressure recordings. The radioactive microsphere technique was used to estimate regional blood flow and cardiac output before (control) and during intravenous (i.v.) infusion of either McN-5691 at three dosage levels (0.3, 1.0, 3.0 mg/kg), or vehicle (VH) at an infusion rate of 0.0408 ml/min. The predominant hemodynamic effect of McN-5691 (cumulative dose = 0.3-4.3 mg/kg i.v.) in conscious SHR was dose-related reduction in mean arterial pressure with normalization occurring at a cumulative dose of 1.3 mg/kg i.v. The antihypertensive effect of McN-5691 was accompanied by reductions in left ventricular peak systolic pressure (cumulative dose = 1.0-4.3 mg/kg i.v.), arterial pressure-rate product (1.3-4.3 mg/kg i.v.), and systemic vascular resistance (4.3 mg/kg i.v.). McN-5691 had no statistically significant effect on heart rate or cardiac contractility as measured by dP/dt/peak left ventricular pressure. The predominant peripheral vascular effects of McN-5691 were increases in skeletal muscle blood flow (4.3 mg/kg i.v.) and reductions in skeletal muscle (1.3-4.3 mg/kg i.v.), renal (1.3-4.3 mg/kg i.v.), gastrointestinal (4.3 mg/kg i.v.), and coronary (1.3-4.3 mg/kg i.v.) vascular resistances. Despite the fall in renal vascular resistance, renal blood flow was not changed by McN-5691. McN-5691 did not have major effects on other regions of the peripheral circulation. Thus, McN-5691 is an antihypertensive agent as defined by its ability to normalize blood pressure in the SHR, and the hemodynamic mechanism leading to this effect is reduction in peripheral vascular resistance. This antihypertensive effect is not accompanied by reflex tachycardia and is not associated with negative inotropic activity or detrimental peripheral circulatory changes in the conscious SHR.

Haemodynamic and regional blood flow changes after acute pulmonary microembolism in conscious rabbits.

The central and peripheral haemodynamic effects of pulmonary embolisation with microspheres were measured in conscious rabbits in which the autonomic and central nervous systems were functioning normally. Sufficient microspheres were given to reduce cardiac output (measured by thermodilution) by one half. This fall in cardiac output was accompanied by a severe fall in arterial pressure and an increase in heart rate and right atrial pressure. Under these conditions cardiac output responded less than normally to an increased right atrial pressure imposed by an infusion of saline. Changes in regional blood flow and resistance were measured with radioactive microspheres injected into the left ventricle. Myocardial blood flow was unaffected by pulmonary embolisation. Cerebral flow was slightly increased. Renal, intestinal, dermal, and skeletal muscle blood flows were all reduced. Myocardial and cerebral tissue vascular resistances decreased; splenic and dermal vascular resistances increased; and renal and skeletal muscle vascular resistances were unchanged.

The role of endogenous opioids in congestive heart failure: effects of nalmefene on systemic and regional hemodynamics in dogs.

We studied the role of endogenous opiates and their interrelationships with the sympathetic nervous system in an experimental preparation of right-sided congestive heart failure (CHF) produced by surgical tricuspid avulsion and progressive pulmonary arterial constriction. Three groups of dogs with CHF and one group of sham-operated dogs were studied. One group of dogs with CHF was given normal saline as pretreatment, while the other two groups were pretreated with either propranolol alone (beta-blockade) or propranolol plus prazosin (alpha- plus beta-blockade). CHF was characterized by weight gain, ascites, elevated right atrial pressure, tachycardia, and reduced cardiac output. Compared with sham-operated animals, animals with CHF exhibited significantly higher baseline levels of plasma beta-endorphin and cortisol. Furthermore, only the animals with CHF responded to the opiate receptor-antagonist nalmefene with significant increases in plasma beta-endorphin, cortisol, and adrenocorticotropic hormone. Administration of nalmefene increased aortic blood pressure, cardiac output, left ventricular dP/dt and dP/dt/P, and blood flow to the myocardium, skeletal muscle, and kidneys in dogs with CHF, but had no appreciable effects in sham-operated dogs. beta-Receptor blockade abolished the increase in cardiac output, left ventricular performance, and blood flow produced by nalmefene, but had no effect on the pressor response to nalmefene. The increase in mean aortic pressure in the beta-blockade group was accompanied by an increase in skeletal muscle vascular resistance. Addition of prazosin in the alpha- plus beta-blockade group abolished the increases in mean aortic pressure and skeletal muscle vascular resistance, suggesting that the changes after propranolol probably resulted from unmasking of alpha-receptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced response of arterioles to oxygen during development of hypertension in SHR.

The goal of this study was to assess the possible role of O2-related local control mechanisms in contributing to an elevated skeletal muscle resistance during the development of hypertension in the spontaneously hypertensive rat (SHR). Diameters of first- (1A), second- (2A), third- (3A), and fourth-order (4A) arterioles were measured by television microscopy in the cremaster muscle of SHR in the early (4- to 6-wk-old) and rapidly developing (8- to 9-wk-old) stages of hypertension and in age-matched normotensive Wistar-Kyoto (WKY) controls. Active neurogenic tone was blocked by superfusing the tissue with 0.1 microgram/ml tetrodotoxin. When superfusion solution PO2 was elevated by changing the gas equilibration mixture from 0 to 5% O2, neurally blocked 3A and 4A of SHR exhibited a significantly greater constriction and a higher incidence of complete closure than those of their age-matched WKY controls. However, there were no significant differences in the constriction of larger arterioles (1A and 2A) in response to elevated superfusion solution PO2. The results suggest that O2-related local control mechanisms could contribute to constriction and closure of small arterioles and to an elevated skeletal muscle vascular resistance early in the development of hypertension in SHR.

Relative contribution of different vascular beds to the pressor effects of alpha-adrenoreceptor agonists and vasopressin in pithed rats: radioactive microsphere determination.

The relative fractional distribution of 51Cr-labelled microspheres was evaluated in pithed rats during equieffective vascoconstrictor responses evoked by infusions of the alpha-adrenoreceptor agonists methoxamine (alpha 1-selective), UK-14,304 (alpha 2-selective) or vasopressin. The proportion of injected radioactive microspheres trapped in each tissue during a sustained pressor response relative to saline treated controls is considered a reflection of the degree of local vascoconstriction in the tissue analysed. All three agonists (methoxamine, UK-14,304 and vasopressin) decreased the number of microspheres trapped in the mesentery and tail. Only methoxamine reduced the blood flow to the kidney and spleen. UK-14,304 did not modify the number of microspheres in the sample of skeletal muscle, however, both vasopressin and methoxamine reduced the blood flow to this tissue. Vasopressin increased the counts in the lungs and particularly in the liver but decreased the number of spheres trapped in the stomach and skin. In contrast to the alpha-adrenoreceptor agonists, vasopressin did not increase the number of microspheres trapped in the heart. Since a reduction in the number of microspheres trapped in the tissue reflects a decrease in blood flow, to that organ it is reasonable to conclude that alpha 1-adrenoreceptor stimulation increases kidney, spleen, mesentery, caudal and skeletal muscle vascular resistance, whereas alpha 2-adrenoreceptors appear to preferentially vasoconstrict the mesenteric and the caudal vascular beds.