Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation

This study examined the hypothesis that formation of endothelium-derived relaxing factor (EDRF) in the brain has a greater influence on basal tone in large arteries than arterioles. Diameters of the basilar artery and its branches and of arterioles on the cerebrum were measured through cranial windows in anesthetized rats. Under control conditions, topical application of NG-monomethyl-L-arginine (L-NMMA), which inhibits formation of EDRF or nitric oxide (NO) from L-arginine, produced concentration-related constriction that was dependent on initial vessel diameter. Large arteries [diameter = 275 +/- 10 microns (mean +/- SE)] constricted by 10.4 +/- 0.8% in response to 10(-5) M L-NMMA. In contrast, arterioles (62 +/- 6 microns) constricted by only 3.7 +/- 0.6% (P less than 0.01 vs. large arteries), regardless of brain region. U-46619 produced similar constriction of large arteries and arterioles, which indicates that reduced responses to L-NMMA in arterioles is not due to impaired constrictor capacity. Sodium nitroprusside produced similar dilatation of large arteries and arterioles, which suggests that activity of guanylate cyclase is not reduced in small vessels. Dilator responses of large arteries and arterioles to acetylcholine, but not nitroprusside, were inhibited by L-NMMA. Thus synthesis of EDRF from L-arginine influences basal tone of cerebral blood vessels, and the effect is greatest in large arteries. In contrast, the role of EDRF or NO in mediating responses to acetylcholine in the cerebral circulation is similar in large arteries and the microcirculation.

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Endothelium-derived relaxing factor in regulation of basal cardiopulmonary and renal function

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.261.2.r323 ◽

1991 ◽

Vol 261 (2) ◽

pp. R323-R328 ◽

Cited By ~ 13

Author(s):

M. A. Perrella ◽

F. L. Hildebrand ◽

K. B. Margulies ◽

J. C. Burnett

Keyword(s):

Renal Function ◽

Competitive Inhibitor ◽

Vehicle Group ◽

Relaxing Factor ◽

Anesthetized Dogs ◽

Endothelium Derived Relaxing Factor ◽

Renal Vascular ◽

Renal Responses

The endothelium has emerged as an important modulator of vascular tone by producing both vasodilating and vasoconstricting substances. In vitro studies have demonstrated that endothelial cells produce endothelium-derived relaxing factor (EDRF), which promotes vasodilation via the stimulation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). However, the role of EDRF in the basal regulation of cardiopulmonary and renal function is not well defined. The present study was therefore designed to assess the function of EDRF by studying two groups of normal anesthetized dogs, of which one received a competitive inhibitor to EDRF generation, NG-monomethyl-L-arginine (L-NMMA; 50 micrograms.kg-1.min-1 iv), and the other received a vehicle. The L-NMMA infusion produced no significant increase in mean arterial pressure but marked increases in systemic, pulmonary, and renal vascular resistances compared with the vehicle group. Although renal blood flow decreased with L-NMMA, no changes were observed in glomerular filtration rate or sodium excretion. Associated with the cardiopulmonary and renal responses with L-NMMA was a modest increase in plasma endothelin (7.9 +/- 1.3 to 10.2 +/- 1.8 pg/ml, P less than 0.05), an endothelium-derived vasoconstrictor. No alteration was observed in plasma or urinary cGMP with EDRF inhibition. These cardiopulmonary and renal responses with L-NMMA may be attributed not only to EDRF inhibition but to an imbalance between endothelium-derived relaxing and contracting factors.

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Role of Endothelium -Derived Relaxing Factor in the Pathogenesis of Coronary Artery Spasm and Its Relationship with Ethanol

Korean Circulation Journal ◽

10.4070/kcj.1992.22.5.768 ◽

1992 ◽

Vol 22 (5) ◽

pp. 768

Author(s):

Jung Don Seo ◽

Jae Kwan Song ◽

Cheol Ho Kim ◽

Dae-Won Sohn ◽

Byung Hee Oh ◽

...

Keyword(s):

Coronary Artery ◽

Coronary Artery Spasm ◽

Relaxing Factor ◽

Endothelium Derived Relaxing Factor

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Endothelium-derived relaxing factor activity in rat lung during hypoxic pulmonary vascular remodeling

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.3.1061 ◽

1993 ◽

Vol 74 (3) ◽

pp. 1061-1065 ◽

Cited By ~ 22

Author(s):

L. Zhao ◽

D. E. Crawley ◽

J. M. Hughes ◽

T. W. Evans ◽

R. J. Winter

Keyword(s):

Hypoxic Pulmonary Vasoconstriction ◽

Hypoxic Exposure ◽

Control Group ◽

Pulmonary Vascular Remodeling ◽

Relaxing Factor ◽

Pulmonary Vasoconstriction ◽

O2 Concentration ◽

Pulmonary Arterial ◽

Endothelium Derived Relaxing Factor

We have investigated the role of endothelium-derived relaxing factor in modulating hypoxic pulmonary vasoconstriction by inhibiting its synthesis with the false substrate NG-monomethyl-L-arginine (L-NMMA) in the isolated blood-perfused lungs of Wistar rats after chronic hypoxia (CH, fractional inspiratory O2 concentration 10%) for 15 h, 2 days, and 7 days. Lungs were perfused with blood of normal hematocrit at constant flow (18 ml/min) ventilated with 1) 95% air-5% CO2 (normoxia) and 2) 2% O2–5% CO2-93% N2 (hypoxia) and were studied in the absence and presence of L-NMMA (30 and 300 microM) or L-arginine (L-Arg, 1 and 6 mM) in separate groups. Pulmonary arterial pressure (Ppa) rose incrementally with hypoxic exposure (all P < 0.05 vs. normoxic control group). Hypoxic pulmonary vasoconstriction (HPV) was markedly reduced after 15 h and 2 days of CH: the mean increases in Ppa (delta Ppa) in hypoxia were 15.3, 3.5, 3.8, and 13.6 mmHg in control rats and rats exposed to 15 h (P < 0.05 vs. control and 7 days of CH), 2 days (P < 0.001 vs. control and 7 days of CH), and 7 days of CH, respectively. Ppa in control rats and rats exposed to 15 h, 2 days, and 7 days of CH were 137, 179, 184, and 166% of control, respectively, after 30 microM L-NMMA (all P < 0.05 when expressed as percent change vs. no L-NMMA). Similar augmentation in HPV was seen after 30 microM L-NMMA, with all hypoxic groups having a greater response than control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

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The role of Ca2+ in the release of endothelium-derived relaxing factor (EDRF)-induced by different agonists

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)60106-x ◽

1990 ◽

Vol 52 ◽

pp. 381

Author(s):

Kigen Kondo ◽

Jane A. Mitchell ◽

John R. Vane

Keyword(s):

Relaxing Factor ◽

Endothelium Derived Relaxing Factor

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Role of Endothelium-Derived Relaxing Factor as a Cardioprotective Agent in Myocardial Ischemia

Endothelium-Derived Contracting Factors ◽

10.1159/000418363 ◽

2015 ◽

pp. 190-197 ◽

Cited By ~ 1

Author(s):

Allan M. Lefer ◽

Phillip S. Tsao ◽

Gerald Johnson

Keyword(s):

Myocardial Ischemia ◽

Relaxing Factor ◽

Endothelium Derived Relaxing Factor

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Role of prostaglandins and endothelium-derived relaxing factor on the renal response to acetylcholine

AJP Renal Physiology ◽

10.1152/ajprenal.1991.260.1.f145 ◽

1991 ◽

Vol 260 (1) ◽

pp. F145-F149 ◽

Cited By ~ 6

Author(s):

M. G. Salom ◽

V. Lahera ◽

J. C. Romero

Keyword(s):

Urine Volume ◽

Urinary Sodium Excretion ◽

Diuretic Effect ◽

Simultaneous Administration ◽

Relaxing Factor ◽

Blocking Effects ◽

Anesthetized Dogs ◽

Endothelium Derived Relaxing Factor ◽

Renal Responses

Acetylcholine (ACh) stimulates the endothelial release of prostacyclin and endothelium-derived relaxing factor (EDRF). However, the relative participation of these substances in mediating the renal effects of ACh remains undefined. To elucidate this issue, we studied the modifications of renal responses to intra-renal ACh infusion (25 ng.kg-1.min-1) produced by blocking the synthesis of EDRF and/or prostaglandins (PG) in anesthetized dogs. ACh induced a significant increase in renal blood flow (RBF) (34%), urine volume (UV) (450%), and urinary sodium excretion (UNaV)(259%), which remained unaltered after blocking the synthesis of EDRF [NG-monomethyl-L-arginine (LNMMA), 50 micrograms.kg-1.min-1 intrarenal] or PG (meclofenamate, 5 mg/kg iv). However, the simultaneous administration of meclofenamate and LNMMA prevented the ACh-induced increase in RBF and UV but not in UNaV. The concomitant infusion of L-arginine but not D-arginine prevented these blocking effects of LNMMA. It was concluded that the ACh-induced increases in RBF and UV, but not UNaV, are mediated by both PG and EDRF. The hemodynamic and diuretic effect of either one of these mediators can be fully compensated during the blockade of the other.

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Role of EDRF/NO in parasympathetic coronary vasodilation following carotid chemoreflex activation in conscious dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.2.h605 ◽

1994 ◽

Vol 267 (2) ◽

pp. H605-H613 ◽

Cited By ~ 7

Author(s):

W. Shen ◽

M. Ochoa ◽

X. Xu ◽

J. Wang ◽

T. H. Hintze

Keyword(s):

Vagus Nerve ◽

Conscious Dogs ◽

Coronary Resistance ◽

Vascular Response ◽

Coronary Vasodilation ◽

Relaxing Factor ◽

Anesthetized Dogs ◽

Endothelium Derived Relaxing Factor ◽

Stimulation Of

The role of endothelium-derived relaxing factor (EDRF) in parasympathetic coronary vasodilation following carotid chemoreflex activation induced by nicotine in conscious dogs and stimulation of the vagus nerve in anesthetized dogs was studied. Injection of nicotine (11 +/- 4 micrograms) into the carotid artery increased coronary blood flow (CBF) by 126 +/- 16% from 28 +/- 3 ml/min and reduced late diastolic coronary resistance (LDCR) by 43 +/- 4% from 3.58 +/- 0.52 mmHg.ml-1.min, accompanied by a significant increase in mean arterial pressure and a decrease in heart rate (all P < 0.01). Pacing and propranolol did not change the coronary vascular response to chemoreflex activation. There were still increases in CBF by 113 +/- 17% from 29 +/- 3 ml/min and decreases in LDCR by 41 +/- 5% from 3.13 +/- 0.52 mmHg.ml-1.min (all P < 0.01). After infusion of N omega-nitro-L-arginine (L-NNA) (30 mg/kg), the increase in CBF following chemoreflex activation was only 23 +/- 3% from 37 +/- 3 ml/min, and the fall in LDCR was 19 +/- 3% from 3.09 +/- 0.51 mmHg.ml-1.min. Stimulation of the vagus nerve showed a relationship between stimulation frequency and coronary vasodilation that was significantly inhibited by L-NNA. Thus EDRF plays an important role in mediating parasympathetic coronary vasodilation during chemoreflex activation and perhaps during many reflexes that cause vagal cholinergic vasodilation in the heart.

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Acetylcholine-induced vasodilatation in rabbit hindlimb in vivo is not inhibited by analogues of L-arginine

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.1.h242 ◽

1991 ◽

Vol 260 (1) ◽

pp. H242-H247 ◽

Cited By ~ 7

Author(s):

A. Mugge ◽

J. A. Lopez ◽

D. J. Piegors ◽

K. R. Breese ◽

D. D. Heistad

Keyword(s):

Substance P ◽

Systemic Blood Pressure ◽

Nitroso Compounds ◽

Femoral Arteries ◽

Relaxing Factor ◽

Resistance Vessels ◽

Basal Tone ◽

Endothelium Derived Relaxing Factor

Nitric oxide (NO) or related nitroso compounds are an endothelium-derived relaxing factor (EDRF), originating from metabolism of L-arginine, L-Arginine analogues with chemically altered guanidino moity are potent and specific inhibitors of EDRF(NO) release. We evaluated effects of two L-arginine analogues, NG-monomethyl-L-arginine (L-NMMA, 100 microM) and N omega-nitro-L-arginine (L-NARG, 30 microM), on acetylcholine-, substance P-, and nitroglycerin-induced relaxation in the blood-perfused rabbit hindlimb in vivo and femoral arteries in vitro. L-NMMA and L-NARG selectively inhibited the vasodilator response to acetylcholine in rabbit femoral arteries in vitro, whereas endothelium-independent response to nitroprusside increased. L-NMMA (1.6 mg/min ia) in the blood-perfused rabbit hindlimb in vivo increased vascular resistance in the hindlimb by 23 +/- 3% (means +/- SE; n = 10) but did not inhibit the vasodilator responses to acetylcholine or substance P. L-NARG (10 mg/kg iv) increased systemic blood pressure by 26 +/- 3% (n = 7) and vascular hindlimb resistance by 22 +/- 9% (n = 8), and blood flow to hindlimb musculature, measured with microspheres, decreased by 46 +/- 5% (n = 6). Pretreatment with L-NARG, however, did not impair vasodilator responses to acetylcholine and substance P. These findings are consistent with the view that basal tone in resistance vessels in the rabbit hindlimb may be mediated by nitroso compounds, whereas agonist-stimulated vasodilation may be mediated by other mechanisms that do not involve the NO-synthesizing enzyme.

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