Analysis of responses to sympathetic nerve stimulation in the feline pulmonary vascular bed

The adrenergic receptor subtypes mediating the response to sympathetic nerve stimulation in the pulmonary vascular bed of the cat were investigated under conditions of controlled blood flow and constant left atrial pressure. The increase in lobar vascular resistance in response to sympathetic nerve stimulation was reduced by prazosin and to a lesser extent by yohimbine, the respective alpha 1- and alpha 2-adrenoceptor antagonists. Moreover, in animals pretreated with a beta-adrenoceptor antagonist to prevent an interaction between alpha- and beta 2-adrenoceptors, responses to nerve stimulation were reduced by prazosin, but yohimbine had no significant effect. On the other hand, in animals pretreated with a beta-adrenoceptor antagonist, yohimbine had an inhibitory effect on responses to tyramine and to norepinephrine. Propranolol had no significant effect on the response to nerve stimulation, whereas ICI 118551, a selective beta 2-adrenoceptor antagonist, enhanced responses to nerve stimulation and injected norepinephrine. The present data suggest that neuronally released norepinephrine increases pulmonary vascular resistance in the cat by acting mainly on alpha 1-adrenoceptors and to a lesser extent on postjunctional alpha 2-adrenoceptors but that this effect is counteracted by an action on presynaptic alpha 2-receptors. The present studies also suggest that neuronally released norepinephrine acts on beta 2-adrenoceptors and that the response to sympathetic nerve stimulation represents the net effect of the adrenergic transmitter on alpha 1-, alpha 2-, and beta 2-adrenoceptors in the pulmonary vascular bed.     

Beta2-microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis

We previously showed that beta2-microglobulin knockout mice treated with anti-asialoGM1 (beta2M/alphaAsGM1 mice) exhibit less hypothermia, reduced production of proinflammatory cytokines, less metabolic acidosis, and improved survival after cecal ligation and puncture (CLP) compared with wild-type mice. The present study was designed to assess hemodynamics and left ventricular contractility at 18 h after CLP. Arterial pressure was measured by carotid artery cannulation, and left ventricular pressure-volume loops were obtained by insertion of a 1.4-F conductance catheter into the left ventricle. Heart rate, stroke volume, and cardiac output were not significantly different between wild-type and beta2M/alphaAsGM1 mice after CLP. However, beta2M/alphaAsGM1 mice exhibited improved mean arterial pressure and systemic vascular resistance compared with wild-type mice. Myocardial function was also better preserved in beta2M/alphaAsGM1 mice as indicated by improved left ventricular pressure development over time, time-varying maximum elastance, endsystolic pressure-volume relationship, and preload recruitable stroke work. Overall, this study shows that cardiovascular collapse characterized by hypotension, myocardial depression, and low systemic vascular resistance occurs after CLP in wild-type mice. However, beta2M/alphaAsGM1 mice exhibit improved hemodynamics and cardiac contractile function after CLP that may account, in part, for our previously observed survival benefit.     

Renal vascular resistance in glomerular diseases--correlation of resistance index with biopsy findings

Duplex Doppler sonography has been recognized as a noninvasive method to evaluate hemodynamic features of renal blood in renal and intrarenal arteries in patients with various renal diseases. The significance of duplex Doppler sonography in the evaluation of renal vascular resistance in glomerular diseases has not yet been clearly determined. The aim of the present study was to evaluate renal vascular resistance in patients with glomerular diseases by measuring intrarenal arterial resistance (RI) and to correlate RI with renal functional tests and other clinical and laboratory data. The Doppler parameters were also correlated with histopathological findings in the kidney which underwent the percutaneous biopsy. Duplex Doppler sonography was used to measure RIs in intrarenal arteries in 50 patients with glomerular diseases and 60 age-matched control subjects. The renal vascular resistance index (RI) was determined by the use of Doppler sonography. The mean RI in 50 patients with glomerular diseases was 0.68 +/- 0.09, which was statistically significantly higher than in 60 control subjects (the mean RI was 0.596 +/- 0.035). In a group of patients with membranoproliferative glomerulonephritis the mean RI was 0.817 +/- 0.624 which was statistically significantly higher than in other groups of glomerulonephritis. The renal vascular (resistance) RI significantly correlated with serum creatinine, creatinine clearance and beta2 microglobulin. Qualitative duplex sonography measure of renal arterial resistance-resistive index does not appear to be reliable in distinguishing different types of glomerulonephritis.     

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

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

TNFalpha and IL-1beta exert no direct vasoactivity in human isolated resistance arteries

The proinflammatory cytokines TNFalpha and IL-1beta are thought to play a role in the mechanism of septic vasodilatory shock. Most evidence indicate that the vascular effects these cytokines are mediated through increased expression of inducible nitric oxide synthase, whereas several animal studies report a more rapid vasorelaxant effect. We studied the direct vascular effects of TNFalpha and IL-1beta in human isolated resistance arteries (n=9) using a microvascular myograph.After precontraction with noradrenaline or a depolarising high potassium solution, TNFalpha and IL-1beta (up to 10(-8) M, alone or in combination) did not exert any relevant vasoactive effect. We conclude that, in contrast with some animal experiments, these cytokines exert no direct vasoactivity in human resistance arteries.     

Effects of hypoxic and CO hypoxia on isolated hearts.

Isolated perfused dog hearts were made hypoxic by respiring the support dog with low oxygen (hypoxic hypoxia) or with carbon monoxide (CO hypoxia). Each heart was exposed to both types of hypoxia, separately. Effects on coronary flow (Qt), coronary vascular resistance, cardiac oxygen consumption (Vo2), and contractility (%deltadP/dt) were studied. Two series of experiments were done. Series I: At constant perfusion pressure. As oxygen content (Cao2) was lowered from 20 to 5 vol%, Qt doubled with hypoxic hypoxia and almost tripled with CO hypoxia (P less than 0.01). Vo2 and contractility increased with both types of hypoxia. Beta-adrenergic blockade eliminated the increase in VO2 and contractility but not the difference in Qt increase between hypoxic and CO hypoxia. Series II: At constant Qt (with beta-blockade), vascular resistance decreased more with CO than hypoxic hypoxia. Finally, alpha-blockade eliminated the difference in vascular resistance and thus with complete (alpha and beta) blockade, the two types of hypoxia have the same effect and are indistinguishable.     

beta(3)-adrenergic stimulation differentially inhibits insulin signaling and decreases insulin-induced glucose uptake in brown adipocytes

Activity of the sympathetic nervous system is an important factor involved in the pathogenesis of insulin resistance and associated metabolic and vascular abnormalities. In this study, we investigate the molecular basis of cross-talk between beta(3)-adrenergic and insulin signaling systems in mouse brown adipocytes immortalized by SV40 T infection. Insulin-induced tyrosine phosphorylation of the insulin receptor, insulin receptor substrate 1 (IRS-1), and IRS-2 was reduced by prestimulation of beta(3)-adrenergic receptors (CL316243). Similarly, insulin-induced IRS-1-associated and phosphotyrosine-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity, but not IRS-2-associated PI 3-kinase activity, was reduced by beta(3)-adrenergic prestimulation. Furthermore, insulin-stimulated activation of Akt, but not mitogen-activated protein kinase, was diminished. Insulin-induced glucose uptake was completely inhibited by beta(3)-adrenergic prestimulation. These effects appear to be protein kinase A-dependent. Furthermore inhibition of protein kinase C restored the beta(3)-receptor-mediated reductions in insulin-induced IRS-1 tyrosine phosphorylation and IRS-1-associated PI 3-kinase activity. Together, these findings indicate cross-talk between adrenergic and insulin signaling pathways. This interaction is protein kinase A-dependent and, at least in part, protein kinase C-dependent, and could play an important role in the pathogenesis of insulin resistance associated with sympathetic overactivity and regulation of brown fat metabolism.     

Involvement of adrenergic receptors in skeletal muscle metabolism of the cold-adapted rat

Hind-limb perfusion was used to investigate alterations of alpha and beta receptor-mediated metabolic effects in cold-adapted (CA) rats. The response to beta receptor stimulation by isoproterenol in the isolated hind-limbs of CA rats was slightly diminished. Oxygen consumption and lactate production were reduced in CA rats after beta receptor stimulation. Noradrenalin infusion caused less vasoconstriction in CA rats than in the controls (CO). Desensitization of alpha and beta receptors due to chronic sympathetic overstimulation may be the underlying cause of these observations. Compared with the controls, metabolism was enhanced in perfused hind-limbs of CA rats with an active nervous system. Decreased vascular resistance due to the lower perfusion pressure in CA rats might contribute to this increased metabolism.     

Estrogen suppresses IL-1beta-mediated induction of COX-2 pathway in rat cerebral blood vessels

Interleukin (IL)-1beta is a potent inducer of inflammatory prostaglandins, which are important mediators of vascular response to cerebral injury, whereas estrogen reduces brain injury in models of ischemic stroke. Thus we examined the effects of in vivo IL-1beta exposure on cerebrovascular cyclooxygenase (COX)-2 expression and function in an animal model of chronic estrogen replacement. Estrogen-treated and nontreated ovariectomized female rats received IL-1beta injections (10 microg/kg i.p.), and then cerebral vessels were isolated for biochemical and contractile measurements. In estrogen-deficient rats, IL-1beta induced cerebrovascular COX-2 protein expression; a peak response occurred 3 h after injection. COX-2 was localized to arterial endothelium using confocal microscopy. IL-1beta increased PGE2 but not PGI2 production and decreased vascular tone as measured in isolated cerebral arteries; the latter effect was partially reversed by treatment with the selective COX-2 inhibitor NS-398 (10 micromol/l). In contrast, in animals treated with estrogen, IL-1beta had no significant effect on COX-2 protein levels, PGE2 production, or vascular tone. Combined treatment with 17beta-estradiol and medroxyprogesterone acetate also prevented increases in PGE2 production after IL-1beta treatment, but treatment with 17alpha-estradiol had no effect. IL-1beta induction of COX-2 protein was prevented by treatment with the nuclear factor-kappaB inhibitor caffeic acid phenethyl ester (20 mg/kg i.p.), and estrogen treatment reduced cerebrovascular nuclear factor-kappaB activity. Estrogen thus has potent anti-inflammatory effects with respect to cerebral vascular responses to IL-1beta. These effects may have important implications for the incidence and severity of cerebrovascular disease.     

The role of beta 2-adrenergic vascular receptors in the peripheral vasodilation caused by 17 beta-estradiol in anesthetized pigs

It has been previously shown in anesthetized pigs that intravenous infusion of 2 microg/h of 17beta-estradiol primarily dilated renal, iliac and coronary circulations, while higher doses of the hormone were required to cause vasodilation also in the mesenteric vascular bed. In the same experimental model, a tonic beta2-adrenoceptor mediated vasodilation, which could be argued to attenuate the vasodilator effect of 17beta-estradiol, has been described. The present study was planned to investigate the role of beta2-adrenergic receptors in the hemodynamic responses of renal and mesenteric vascular beds to 17beta-estradiol. Changes in flow caused by intravenous infusion of 2 microg/h of the hormone at constant heart rate and aortic blood pressure in the left renal and superior mesenteric arteries were assessed using electromagnetic flowmeters. In six pigs, infusion of 17beta-estradiol caused an increase in renal blood flow, which averaged 12.1% of the control values, without affecting mesenteric blood flow. In the same pigs, after hemodynamic variables had returned to the baseline values, blockade of beta2-adrenergic receptors with butoxamine caused an increase in aortic blood pressure and an increase in renal and mesenteric resistance. The subsequent infusion of 17beta-estradiol elicited increases in renal and mesenteric blood flow which respectively averaged 19.6% and 12.8%. Therefore, the present study in anesthetized pigs have shown that the vasodilator responses of the renal and mesenteric circulations to 17beta-estradiol were attenuated and even masked by a tonic beta2-adrenoceptor mediated vasodilation. This indicates that some vasodilator effects elicited by normally used replacement doses of the hormone may not be apparent.     

beta(2)-glycoprotein I protects J774A.1 macrophages and human coronary artery smooth muscle cells against apoptosis

beta(2)-Glycoprotein I (beta(2)-GPI) is a plasma glycoprotein with multifactorial relevance to clinical consequences. It was previously indicated that beta(2)-GPI can selectively bind to apoptotic cells. This study was designed to determine the role of beta(2)-GPI in apoptosis. Using an immunohistochemical study, we observed that beta(2)-GPI was co-localized with the apoptotic macrophages and smooth muscle cells (SMCs) of human coronary arteries. The contribution of beta(2)-GPI to apoptotic death was then investigated in vascular cells. Two nitric oxide (NO) donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl penicillamine (SNAP) were used in this study to trigger apoptosis in J774A.1 macrophages and human coronary artery smooth muscle cells (HCASMC). Cell viability was significantly improved in beta(2)-GPI-treated cells. It was also possible to detect a remarkable inhibitory effect by beta(2)-GPI on the NO-induced apoptosis by preventing nuclear shrinkage. Furthermore, the NO-induced apoptosis was associated with increase in caspase-3 activity and in the protein levels of caspase-3, c-Fos, and c-Jun. However, all these apoptosis-related events were inhibited in vascular cells treated with 200 microg/ml beta(2)-GPI. This is the first study to show that beta(2)-GPI may be important in the prevention of apoptosis in vascular cells.     

Cytokines and vascular reactivity in resistance arteries

Cytokine levels are elevated in many cardiovascular diseases and seem to be implicated in the associated disturbances in vascular reactivity reported in these diseases. Arterial blood pressure is maintained within a normal range by changes in peripheral resistance and cardiac output. Peripheral resistance is mainly determined by small resistance arteries and arterioles. This review focuses on the effects of cytokines, mainly TNF-alpha, IL-1beta, and IL-6, on the reactivity of resistance arteries. The vascular effects of cytokines depend on the balance between the vasoactive mediators released under their influence in the different vascular beds. Cytokines may induce a vasodilatation and hyporesponsiveness to vasoconstrictors that may be relevant to the pathogenesis of septic shock. Cytokines may also induce vasoconstriction or increase the response to vasoconstrictor agents and impair endothelium-dependent vasodilatation. These effects may help predispose to vessel spasm, thrombosis, and atherogenesis and reinforce the link between inflammation and vascular disease.     

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

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

Stimulation of genetic resistance to marrow grafts in mice by interferon-alpha/beta

Lethally irradiated mice were infused with syngeneic, H-2 allogeneic, parental strain, or H-2 heterozygous bone marrow cells. They were injected daily with rabbit anti-mouse interferons (IFN)-alpha/beta or gamma or with IFN-alpha/beta. The growth of donor-derived cells was judged 5 days later by measuring splenic incorporation of 5-iodo-2'-deoxyuridine-125I into DNA. Antibodies to IFN-alpha/beta, but not to IFN-gamma, weakened genetic (both hybrid and allogeneic) resistance to marrow cell grafts. IFN-alpha/beta stimulated hybrid and allogeneic resistance, the latter even in genetically "poor responder" mice. Mice pretreated with silica, which weakens genetic resistance, were stimulated by IFN-alpha/beta to resist incompatible marrow cell grafts; however, IFN-alpha/beta failed to reverse the effects of antiasialo GM1 serum on marrow graft rejection. IFN-alpha/beta did not inhibit the growth of syngeneic marrow cells and did not stimulate resistance to H-2 heterozygous bone marrow cells. We propose that genetic resistance occurs in two discrete steps. In the first step, hemopoietic histocompatibility (Hh) antigens are recognized by one host cell type, and this recognition leads to IFN-alpha/beta secretion by a silica-sensitive cell. In the second step, asialo GM1-positive natural killer cells stimulated by IFN-alpha/beta recognize Hh antigens on marrow stem cells and cause rejection. The defects in resistance observed in genetically poor responder mice and in mice treated with silica appear to involve the first step in recognition. The lack of rejection of H-2 heterozygous (Hh-) marrow cells by parental strain mice injected with IFN-alpha/beta indicated that specific Hh recognition is critical in the second step of genetic resistance.     

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

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

Nervous control of the branchial vascular resistance of the Atlantic cod,Gadus morhua

Summary The effects on branchial vascular resistance of electrical stimulation of the nervous supply to the gills of the Atlantic cod were studied in constant pressure perfused gill preparations.Stimulation of the right sympathetic chain immediately anterior to the coeliac ganglion produces either a -adrenoceptor mediated decrease in branchial vascular resistance of the gill arches on the right side, or an -adrenoceptor mediated increase which is reversed by phentolamine to a -adrenoceptor mediated decrease in branchial vascular resistance.Stimulation of the entire vago-sympathetic nerve trunk to the third isolated gill arch produces an increase in branchial vascular resistance, which in some preparations can be reversed by atropine to a -adrenoceptor mediated decrease. A second type of constrictory innervation of vagal origin (non-adrenergic, non-cholinergic) may be concluded from the lack of blocking capacity of cholinergic and adrenergic antagonists.It is concluded that the branchial vascular bed of the cod is controlled by both sympathetic (dilatory and sometimes also constrictory) and parasympathetic (constrictory) fibres. The site of action of the nerve supply on the various effectors of the complex vasculature of the gills is not known. An autonomic innervation with its direct, rapid and restricted effects may reinforce the more general effects of circulating vaso-active substances.     

Endothelin produces pulmonary vasoconstriction and systemic vasodilation

Endothelin is a newly described polypeptide derived from endothelial cells. The effects of porcine endothelin on the pulmonary vascular bed and systemic vascular bed were investigated in the anesthetized, intact-chest cat under conditions of constant pulmonary blood flow and left atrial pressure. Intralobar bolus injections of porcine endothelin (100-1000 ng) produced a mild vasoconstrictor response in the pulmonary vascular bed. The pulmonary vasoconstrictor response to endothelin was not altered when pulmonary vasomotor tone was increased by infusion of U46619. In contrast to this mild pulmonary vasoconstrictor response, endothelin decreased systemic arterial pressure. Moreover, injections of porcine endothelin into the right and left atria produced similar reductions in aortic pressure as well as similar increases in cardiac output and decreases in systemic vascular resistance. The systemic vasodilator response to porcine endothelin was not affected by beta 2-adrenoceptor blockade. The present data suggest that endothelin does not undergo significant first-pass pulmonary metabolism. The pulmonary vasoconstrictor response to bolus injections of porcine endothelin is not altered by changes in pulmonary vasomotor tone. In contrast, endothelin markedly dilated the systemic vascular bed independently of activation of beta 2-adrenoceptors. The present study provides the first report of the activity of endothelin on pulmonary and systemic hemodynamics in vivo. Moreover, the potent vasodilator activity of endothelin in the systemic vascular bed and its weak effect on pulmonary vessels suggest that endothelin may be more important in the regulation of peripheral vasomotor tone than the pulmonary vascular bed.     

The effect of beta-adrenergic blockade on leg blood flow with repeated maximal contractions of the triceps surae muscle group in man

The effect of beta-adrenergic blockade on torque output and leg blood flow was examined in seven healthy young men during repeated maximal isometric voluntary contractions of the triceps surae muscle group. Exercise was performed in either a bent- or straight-leg position during each of four drug treatments: placebo, propranolol, metoprolol, oxprenolol. Contractions were sustained for 5 s with 5 s relaxation for a total of 10 min followed by a 10-min recovery. Leg blood flow was measured during the 5 s relaxation separating contractions using strain gauge plethysmography. Torque output decreased during the 10-min contractions with no differences between the four drug treatments. Leg blood flow was lower with beta-blockade during the initial stages of exercise and recovery in the bent-leg position but no differences were observed after 3 min exercise or recovery. Leg blood flow in the straight-leg position was not different between any of the four drug treatments, but it was significantly less than in bent-leg exercise. The lower blood flows during the initial stages of exercise in the beta-blocked conditions probably reflect a slowing of the central cardiovascular response because of beta 1-receptor blockade of the heart rather than on the beta 2-receptors effects on peripheral vascular resistance. It is concluded that local vasodilator substances released from the working muscle may play a more important role than beta 2-receptor stimulation of smooth muscle in skeletal muscle resistance vessels in regulating local muscle blood flow during maximal exercise of the triceps surae muscle group.     

Role of beta 2-adrenergic receptors on coronary resistance during exercise

The effects of regional alpha- and specific beta 2-adrenergic receptor blockade on measurements of late diastolic coronary resistance (LDCR) and mean coronary blood flow velocity (CBFV) during exercise were examined in 14 conscious adult mongrel dogs. Specific beta 2-adrenergic receptor blockade (ICI 118.551) significantly decreased CBFV and increased LDCR by blockade of beta 2-vasodilator tone independent of alpha-adrenergic receptor-mediated tone and independent of altering myocardial metabolism. alpha-Adrenergic receptor blockade (phentolamine, 1 mg) significantly increased CBFV and decreased LDCR by blocking sympathetically mediated vasoconstrictor tone. There was no significant difference in the magnitude of response between alpha- and beta 2-adrenergic receptor blockade. These results demonstrate that alpha- and beta 2-adrenergic receptors have a significant and evidently equal influence on CBFV and LDCR during exercise. Four weeks of daily exercise and left stellate ganglionectomy (LSGx) prevented phentolamine-induced vasodilation but not ICI 118.551-induced vasoconstriction. This suggests that daily exercise and LSGx significantly decreased the alpha-adrenergic receptor-mediated vasoconstrictor tone on the coronary circulation, resulting in an apparently greater role for the coronary vascular beta 2-adrenergic receptor on the control of CBFV and LDCR during exercise.     

Comparison of haemodynamic responses to dobutamine and salbutamol in cardiogenic shock after acute myocardial infarction.

Nine patients with critically reduced cardiac output after acute myocardial infarction underwent a single cross-over comparison of dobutamine and salbutamol to compare the haemodynamic effects of these drugs, which have, respectively, predominantly beta 1-adrenergic and beta 2-adrenergic agonist activity. The responses were used to select the more appropriate treatment for individual patients. Only relatively small responses were obtained: those with poorest baseline measurements tended to show the least effect. When the results from the series were averaged, dobutamine (250-750 microgram/min) caused a small but progressive increase in cardiac index (1.8 to 2.2 1/min/m2) throughout the dose range. Systemic blood pressure was not increased, and calculated systemic vascular resistance fell from 25 to 19 units. Heart rate rose from 107 to 118 beats/min and stroke index from 17 to 19 ml/beat/m2. Pulmonary artery end-diastolic pressure fell from 18 to 15 mm Hg. Salbutamol (10-40 microgram/min) produced a similar progressive increase in cardiac index, from 1.6 to 2.21/min/m2. Systemic blood pressure was not altered, and systemic vascular resistance fell from 25 to 20 units. Heart rate rose from 105 to 119 beats/min and stroke index from 16 to 19 ml/beat/m2. Pulmonary artery end-diastolic pressure did not fall. Dobutamine and salbutamol have closely similar haemodynamic effects when used in cardiogenic shock after acute myocardial infarction. Both drugs increase cardiac index but heart rate also rises, and the increase in stroke index is relatively small. Mean arterial pressure is altered little by either agent, but dobutamine (in contrast with dopamine) tends to reduce pulmonary artery end-diastolic pressure, which may be beneficial.