NO is involved in MCh-induced accentuated antagonism via type II PDE in the canine blood-perfused SA node

2000 ◽  
Vol 279 (5) ◽  
pp. H2509-H2518 ◽  
Author(s):  
Shingo Sasaki ◽  
Kazuyuki Daitoku ◽  
Atsushi Iwasa ◽  
Shigeru Motomura
Keyword(s):  
Sinoatrial Node ◽  
Pacemaker Activity ◽  
Type Ii ◽  
Arterial Infusion ◽  
Arterial Blood ◽  
Endogenous Nitric Oxide ◽  
Camp Hydrolysis ◽  
The Right ◽  
Dose Dependent

The possible role of type II (cGMP-stimulated cAMP hydrolysis) phosphodiesterase (PDE) in the accentuated antagonism of muscarinic effects on heart rate during β-stimulation via endogenous nitric oxide (NO) was evaluated. The canine isolated sinoatrial node preparation was cross circulated with arterial blood of a support dog. The sinoatrial rate of the preparation was 96 ± 5 beats/min ( n = 16) at control. Methacholine (MCh; 0.01–1 μg) injected into the right coronary artery in a bolus fashion caused dose-dependent decreases in sinoatrial rate. Under an intra-arterial infusion of isoproterenol (1 μM), resulting in ∼50% increase in sinoatrial rate, MCh-induced decreases were markedly augmented from −18 ± 3% to −44 ± 4% at 0.3 mg of MCh. When N G-nitro-l-arginine methyl ester (100 μM) or N G-monomethyl-l-arginine (100 μM) were continuously infused, the augmented MCh-induced decreases in sinoatrial rate were significantly suppressed (−29 ± 3% or −25 ± 3%, respectively, P < 0.01). Pretreatment with either 3-isobutyl-1-methylxanthine (IBMX; 20 μM), a non-selective PDE inhibitor, or amrinone (20 μM), a selective type III (cGMP inhibited cAMP hydrolysis) PDE inhibitor, doubled the isoproterenol-induced increase in the sinoatrial rate. However, the augmented MCh-induced decreases in sinoatrial rate were significantly depressed by IBMX (from −23 ± 5% to −14 ± 1%, P < 0.01) but not by amrinone (to −20 ± 3%). These results suggest that MCh-induced accentuated antagonism in the sinoatrial node pacemaker activity can be modulated by endogenous NO via an activation of the type II cyclic GMP-stimulated cAMP PDE.

Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure

2005 ◽  
Vol 288 (5) ◽  
pp. H2332-H2341 ◽  
Author(s):  
Hong Zheng ◽  
Yi-Fan Li ◽  
Kurt G. Cornish ◽  
Irving H. Zucker ◽  
Kaushik P. Patel
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Exercise Training ◽  
Paraventricular Nucleus ◽  
No Donor ◽  
Protein Levels ◽  
Arterial Blood ◽  
Endogenous Nitric Oxide ◽  
Dose Dependent

Previously, we have demonstrated that an altered endogenous nitric oxide (NO) mechanism within the paraventricular nucleus (PVN) contributes to increased renal sympathetic nerve activity (RSNA) in heart failure (HF) rats. The goal of this study was to examine the effect of exercise training (ExT) in improving the endogenous NO mechanism within the PVN involved in the regulation of RSNA in rats with HF. ExT significantly restored the decreased number of neuronal NO synthase (nNOS)-positive neurons in the PVN (129 ± 17 vs. 99 ± 6). nNOS mRNA expression and protein levels in the PVN were also significantly increased in HF-ExT rats compared with HF-sedentary rats. To examine the functional role of NO within the PVN, an inhibitor of NOS, NG-monomethyl-l-arginine, was microinjected into the PVN. Dose-dependent increases in RSNA, arterial blood pressure (BP), and heart rate (HR) were produced in all rats. There was a blunted increase in these parameters in HF rats compared with the sham-operated rats. ExT significantly augmented RSNA responses in rats with HF (33% vs. 20% at the highest dose), thus normalizing the responses. The NO donor sodium nitroprusside, microinjected into the PVN, produced dose-dependent decreases in RSNA, BP, and HR in both sham and HF rats. ExT significantly improved the blunted decrease in RSNA in HF rats (36% vs. 17% at the highest dose). In conclusion, our data indicate that ExT improves the altered NO mechanism within the PVN and restores NO-mediated changes in RSNA in rats with HF.

scholarly journals Immune Thromboses of the Pulmonary Vessels

1977 ◽  
Author(s):  
S.V. Andreev ◽  
A.A. Kubatiev
Keyword(s):  
Right Ventricle ◽  
Vascular Wall ◽  
True Nature ◽  
Pulmonary Vessels ◽  
Arterial Blood ◽  
Compensatory Hyperfunction ◽  
Antigenic Complex ◽  
Pulmonary Arterial ◽  
The Right

According to current concepts, pathogenesis of intravascular trombus formation is underlaid by three crucial factors: lesion of the vascular wall, impairment of hemodynamics and hemostatic properties of the blood. While admitting the important role of each of these factors, one should acknowledge that the true nature of thrombosis is much more complicated and does not always fit the framework of this triad. In our experiments on rabbits, it was demonstrated that the thrombotic process in the basin of the pulmonary vessels could be successfully reproduced even in intact animals under conditions of disturbed immune homeostasis. A distinctive feature of immune thrombosis of the pulmonary vessels was a generalized lesion of the microcirculatory bed, gradual increase in the thrombotic masses and involvement of the major branches of the pulmonary vessels (PV). Morphologically, a picture of lymphoid-cellular infiltration and localization of the antigenic complex in the affected PV was revealed. As a result of progressive decrease in the pulmonary arterial blood circulation and increasing resistance in the system of the lesser circulation there were noted, already during the first hours after the onset of the capillary thrombosis, a compensatory hyperfunction of the right ventricle of the heart which was manifested in its highly increased contractility, higher levels of cyclic AMP and phosphorylation potential. At a later period, however, the compensatory possibilities of the right ventricle of the heart failed to overcome this resistance with resulting incompetence of the organ starting to develop within 2-3 days.

Gastric microvascular actions of platelet-activating factor: role of leukocytes

1992 ◽  
Vol 262 (3) ◽  
pp. G537-G544
Author(s):  
J. G. Wood ◽  
Z. Y. Yan ◽  
L. Y. Cheung
Keyword(s):  
Vascular Resistance ◽  
Perfusion Pressure ◽  
Ex Vivo ◽  
Platelet Activating Factor ◽  
Arterial Infusion ◽  
Edema Formation ◽  
Arterial Blood ◽  
Anesthetized Dogs ◽  
Alpha Chloralose

This study examined the effects of platelet-activating factor (PAF) on the gastric microcirculation. We measured changes in vascular resistance and filtration during intra-arterial infusion of graded doses of PAF and its metabolite, lyso-PAF, to an ex vivo gastric segment of alpha-chloralose-anesthetized dogs. PAF produced dose-related sustained increases in vascular resistance (2-150 nM; n = 6). Filtration and venous hematocrit were also both significantly increased by PAF. In contrast, there were no statistically significant changes in these measurements with lyso-PAF (n = 6). Filtration and venous hematocrit were not significantly changed by norepinephrine at doses that increased perfusion pressure to the same degree as PAF (n = 4). PAF also increased filtration in the absence of changes in perfusion pressure (during maximal vasodilation induced with papaverine). Finally, removal of leukocytes from gastric arterial blood significantly attenuated these responses to PAF. Our results suggest that PAF-induced mucosal ischemia is primarily due to vasoconstriction and may involve edema formation due to increased filtration as well. In addition, these responses to PAF appear to be largely dependent on circulating leukocytes.

ANP has no postsynaptic effect on autonomic regulation of cardiac pacemaker rate in the rat

1993 ◽  
Vol 265 (6) ◽  
pp. H1983-H1987 ◽  
Author(s):  
D. J. Atchison ◽  
P. S. Pennefather ◽  
U. Ackermann
Keyword(s):  
Salt Solution ◽  
Action Potentials ◽  
Sinoatrial Node ◽  
Cardiac Pacemaker ◽  
Pacemaker Activity ◽  
Physiological Salt Solution ◽  
Sprague Dawley ◽  
Pacemaker Cells ◽  
Frequency Of Action Potentials ◽  
The Right

We studied whether atrial natriuretic peptide (ANP) influences sinoatrial node pacemaker activity or whether it modifies the response to activation of postsynaptic autonomic receptors. Male Sprague-Dawley rats were anesthetized with pentobarbital sodium (45 mg/kg). Their hearts were removed quickly and placed in physiological salt solution. The atria were isolated; the right intra-atrial chamber was exposed to allow intracellular recording from sinoatrial node pacemaker cells. The tissue was placed in a temperature-regulated recording chamber and superfused with warmed oxygenated physiological salt solution. With use of standard microelectrode recording techniques, action potentials were recorded from spontaneously depolarizing cells in the presence of muscarine (62.5–500 nM) or norepinephrine (0.1 and 1.0 microM). Muscarine reduced the frequency of action potentials dose dependently, whereas norepinephrine increased their frequency. The addition of ANP (0.1–100 nM) to the superfusion had no effect on the frequency of action potentials during the superfusion of physiological salt solution or in the presence of either muscarine or norepinephrine. We conclude that ANP does not act on cardiac pacemaker cells to modulate the effect of neurotransmitters.

Role of endogenous nitric oxide in progression of atherosclerosis in apolipoprotein E-deficient mice

2000 ◽  
Vol 278 (5) ◽  
pp. H1679-H1685 ◽  
Author(s):  
Katalin Kauser ◽  
Valdeci da Cunha ◽  
Richard Fitch ◽  
Cornell Mallari ◽  
Gabor M. Rubanyi
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Apolipoprotein E ◽  
Lesion Size ◽  
Significant Inhibition ◽  
Arterial Blood ◽  
Endogenous Nitric Oxide ◽  
Progression Of Atherosclerosis ◽  
Apoe Ko

This study investigated the role of endogenous nitric oxide (NO) in the progression of atherosclerosis in apolipoprotein E-deficient [apoE-knockout (KO)] mice. Mice were treated with N ω-nitro-l-arginine methyl ester (l-NAME) an inhibitor of nitric oxide synthase (NOS) or with the NOS substrate l-arginine for 8 wk.l-NAME treatment resulted in a significant inhibition of NO-mediated vascular responses and a significant increase in the atherosclerotic plaque/surface area in the aorta of apoE-KO mice.l-arginine treatment had no influence on endothelial function and did not alter lesion size. Mean arterial blood pressure and serum lipid levels were not altered by the treatments. At the beginning of the study impairment in endothelial function was only apparent in the case of N G-nitro-l-arginine-induced, NO-mediated contraction, whereas ACh-induced, NO-mediated relaxation was not different between age-matched apoE-KO and C57Bl/6J mice. After the 8-wk treatment with the NOS inhibitor, both NO-mediated responses were significantly inhibited. The acceleration in lesion size concomitant to the severely impaired NO-mediated responses indicates that lack of endogenous NO is an important progression factor of atherosclerosis in the apoE-KO mouse.

An Arg-Gly-Asp peptide stimulates constriction in rat afferent arteriole

1997 ◽  
Vol 273 (5) ◽  
pp. F768-F776 ◽  
Author(s):  
Kay-Pong Yip ◽  
Donald J. Marsh
Keyword(s):  
Smooth Muscle ◽  
Rat Kidney ◽  
No Production ◽  
Afferent Arteriole ◽  
Calcium Dependent ◽  
Endogenous Nitric Oxide ◽  
Arginine Glycine Aspartic Acid ◽  
Dose Dependent ◽  
Α Subunits

The potential role of integrins in the myogenic mechanism was studied in the rat afferent arteriole (AA) by fluorescence immunolocalization and microperfusion of isolated AA. Confocal fluorescence images were acquired from frozen sections of rat kidney after indirect immunostaining for various integrin β- and α-subunits. The β1-, β3-, α3-, α5-, and αV-integrins were found on the plasma membrane in smooth muscle of AA, providing the morphological basis for participation of integrins in mechanotransduction. With 1 mM nitro-l-arginine methyl ester (l-NAME) in the luminal perfusate to inhibit endogenous nitric oxide (NO) production from AA, the hexapeptide GRGDSP (10−7–10−3 M) induced immediate vasoconstriction. The constriction was dose dependent and specific for peptides with arginine-glycine-aspartic acid (RGD) motifs, commonly found on the binding sites of extracellular matrix to integrins. In controls, the hexapeptide GRGESP induced no constriction. GRGDSP, 1 mM, induced a 21.6 ± 2.6% decrease ( P < 0.05, n = 6) in lumen diameter for 30 s and an 18.3 ± 4.1% increase ( P < 0.05, n = 6) in smooth muscle intracellular calcium concentration for 18 s, as measured by the emission ratio of Fluo-3/Fura Red. Binding of exogenous RGD motifs with exposed integrins on AA smooth muscle therefore triggers calcium-dependent vasoconstriction. However, the dose response to RGD was not sensitive to the myogenic tone of the vessel, which suggests that the integrin-mediated vasoconstriction is different from myogenic constriction.

Evidence that dopamine-2 mechanisms control renal function

1990 ◽  
Vol 259 (5) ◽  
pp. F793-F800 ◽  
Author(s):  
H. M. Siragy ◽  
R. A. Felder ◽  
N. L. Howell ◽  
R. L. Chevalier ◽  
M. J. Peach ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Urinary Flow ◽  
Plasma Aldosterone Concentration ◽  
Arterial Blood ◽  
Ly 171555 ◽  
Renal Vascular ◽  
Dose Dependent

Dopamine is synthesized by the kidney, and dopamine-2 (DA2) receptors are present in the renal glomerulus. However, no role for DA2 receptors in the kidney has been defined. We investigated the possible role of DA2 receptors in control of renal function by intrarenal infusion of a highly specific DA2 antagonist YM-09151 (YM), in conscious uninephrectomized dogs (n = 5) in metabolic balance at Na intake 40 meq/day. YM infused at 0.01 pmol.kg-1.min-1 did not cause any changes in urinary flow rate or Na excretion. Administration of YM (infusions from 0.1 to 10.0 pmol.kg-1.min-1) caused a significant dose-dependent diuresis (F = 20.3; P less than 0.001) and natriuresis (F = 35.2; P less than 0.0001) and an increase in glomerular filtration rate (F = 45.4; P less than 0.0001), renal plasma flow (F = 209.3; P less than 0.0001), and filtration fraction (F = 11.2; P less than 0.0001). No significant changes in plasma renin activity, plasma aldosterone concentration, or mean arterial blood pressure occurred with any of the doses of YM infused into the renal artery. Coinfusion of LY-171555, a specific DA2 agonist, at a dose that itself did not affect renal function, completely abrogated the renal hemodynamic and excretory changes induced by YM. The data suggest that dopamine produced intrarenally may act at renal vascular and/or glomerular DA2 receptors to control renal function.

Role of endothelium-derived relaxing factor in active hyperemia of the canine diaphragm

1992 ◽  
Vol 72 (6) ◽  
pp. 2393-2401 ◽  
Author(s):  
S. N. Hussain ◽  
D. J. Stewart ◽  
J. P. Ludemann ◽  
S. Magder
Keyword(s):  
Vascular Resistance ◽  
Systemic Circulation ◽  
Mechanically Ventilated ◽  
Relaxing Factor ◽  
Arterial Blood ◽  
Left Diaphragm ◽  
Phrenic Artery ◽  
Endothelium Derived Relaxing Factor ◽  
Dose Dependent

To assess the effect of endothelium-derived relaxing factor (EDRF) on diaphragmatic vascular resistance at rest and during contractions, we studied an in situ isolated diaphragm preparation in anesthetized and mechanically ventilated dogs. The arterial supply of the left diaphragm (phrenic artery) was catheterized and perfused with arterial blood at a fixed flow rate. Drugs were infused through a side port of the arterial catheter at 1/100th of the phrenic arterial flow. The inferior phrenic vein was catheterized to complete the isolation from the systemic circulation. Three sets of experiments were performed. In set 1 (n = 3), we infused endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) dilators at increasing concentrations. ACh and SNP infusion elicited a dose-dependent decline in phrenic vascular resistance (Rphr) at concentrations greater than 10(-8) M and 0.50 micrograms/ml, respectively. In set 2 (n = 15), we infused an inhibitor of EDRF synthesis and release, L-argininosuccinic acid (ArgSA), at increasing concentrations (10(-4), 3 x 10(-4), and 6 x 10(-4) M). ArgSA produced a dose-dependent increase in Rphr. Infusion of another EDRF inhibitor (NG-nitro-L-arginine, LNA, 6 x 10(-4) M) elicited increase in Rphr similar to that induced by ArgSA. In set 3 (n = 25), we infused ArgSA or LNA (6 x 10(-4) M) simultaneously with ACh and SNP and during sustained (2-Hz) contractions of the diaphragm. Both ArgSA and LNA completely reversed ACh vasodilation, whereas SNP vasodilation was reversed by 26 and 11%, respectively. ArgSA or LNA infusion during contractions reversed vasodilation by 48 and 52%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of adrenal arterial infusion of P-113 on aldosterone secretion in Na-deficient sheep

1979 ◽  
Vol 236 (4) ◽  
pp. F333-F341
Author(s):  
J. R. Blair-West ◽  
J. P. Coghlan ◽  
D. A. Denton ◽  
K. J. Hardy ◽  
B. A. Scoggins ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Gland ◽  
Renin Angiotensin System ◽  
Blood Levels ◽  
Aldosterone Secretion ◽  
Arterial Infusion ◽  
Sodium Deficiency ◽  
Arterial Blood ◽  
Conscious Sheep

To examine the role of the renin-angiotensin system in aldosterone regulation, P-113 ([Sar1,Ala8]angiotensin II) was infused into the arterial blood supply of the transplanted adrenal gland in conscious sheep. Effects on the aldosterone response to infused angiotensin II and III in sodium-replete sheep were compared with effects of P-113 on aldosterone secretion in sodium deficiency. P-113 infusion up to 1,000 microgram/h for 1-2 h did not consistently alter aldosterone secretion in sodium-deficient sheep. However, in sodium-replete sheep P-113 infusion for 20 min at 10 microgram/h or more abolished aldosterone responses to high blood levels of angiotensin II and III produced by systemic intravenous or adrenal intra-arterial infusion. P-113 infusions alone had minor agonist activity on aldosterone secretion in sodium-replete sheep. These results indicate that the increased secretion of aldosterone in Na-depleted sheep is not simply and commensurately determined by increase of angiotensin II and III concentration in the arterial blood perfusing the adrenal gland.

Reduction of intrinsic sinoatrial frequency and norepinephrine response of the exercised rat

1977 ◽  
Vol 55 (4) ◽  
pp. 813-820 ◽  
Author(s):  
Richard L. Hughson ◽  
John R. Sutton ◽  
J. Desmond Fitzgerald ◽  
Norman L. Jones
Keyword(s):  
Sinoatrial Node ◽  
Parasympathetic Nervous System ◽  
Control Group ◽  
Response Curves ◽  
Chronotropic Response ◽  
In Vitro Measurements ◽  
The Right

Physical training is associated with a reduction of intrinsic sinoatrial activity; the present study examined the role of the parasympathetic nervous system in this reduction. Six groups of rats were studied for 10 weeks: inactive control; treadmill exercised; parasympathetic receptor blockade with atropine; exercise plus atropine; parasympathetic receptor stimulation with carbachol; and exercise plus carbachol. In vivo ISF (cardiac frequency 20 min after injection of propranolol and atropine) was measured at 3-week intervals. At the end of 10 weeks the right atrium was excised, in vitro measurements were made of ISF, and chronotropic dose–response curves to acetylcholine and norepinephrine were established. In vivo, ISF was reduced with time, the greatest reduction being found in the exercise plus atropine group; the treadmill-exercised and the atropine-treated groups also had a greater reduction than the control group. In vitro, no differences were observed in acetylcholine responses. The maximum norepinephrine chronotropic response was reduced in the treadmill-exercised and the exercise plus atropine groups. The maximum norepinephrine-induced frequency correlated with the in vitro ISF (r = 0.75). Thus, ISF was reduced with training, but this effect was independent of parasympathetic activity. The properties of the sinoatrial node which set ISF also influenced the maximum norepinephrine response.

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