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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary artery disease (CAD) has been documented to be usually associated with endothelial dysfunction. Thus, the present experiments were performed to investigate whether non-hypotensive doses of calcium antagonists can compensate for the effects of deficient endogenous formation of nitric oxide (NO) in the coronary vascular bed in vivo. In chronically instrumented conscious dogs (n = 6) which were prepared for the measurement of coronary blood flow (CBF), coronary diameter of the left circumflex artery (LCX), mean arterial blood pressure (MAP) and heart rate (HR), continuous intravenous infusions of 0.2 micrograms/kg/min nisoldipine (NI) or 2.0 micrograms/kg/min diltiazem (DT) were performed after intracoronary pretreatment with either vehicle or the inhibitor of NO synthesis NG-nitro-L-arginine methyl ester (L-NAME, 6 mg/kg). NI dose-dependently increased CBF up to a maximum of +74 +/- 7.5% from control, while LCX diameter and HR were not significantly affected. MAP fell slightly (-5 +/- 3 mmHg). The maximum CBF increase in response to diltiazem at 10-fold higher doses was +39 +/- 13% while MAP fell -12 +/- 2 mmHg at the highest cumulative dose (100 micrograms/kg). HR and LCX diameter remained unaltered. Pretreatment with L-NAME caused marked hypertension and bradycardia, associated with reduction in CBF (-34 +/- 16%) and LCX diameter (-9.5 +/- 0.8%). Subsequent infusion of NI or DT increased CBF up to the control values obtained before L-NAME. In contrast, both calcium antagonists failed to reverse the effects on MAP or HR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low dose calcium-antagonism compensates for impaired myocardial blood supply resulting from deficient nitric oxide synthesis. 799 Sep 75

1. The effects of the inhibitor of nitric oxide (NO) synthesis, NG-nitro-L-arginine methyl ester (L-NAME), on systemic arterial blood pressure and jejunal motility, blood flow, and oxygen uptake have been investigated in anaesthetized dogs. 2. L-NAME (cumulative doses of 0.1-20 mg kg-1, i.v.) dose-dependently increased blood pressure and jejunal motility and decreased heart rate. The maximal response of these three variables occurred at doses, 3, 10 and 10 mg kg-1, respectively. L-NAME (cumulative doses of 0.5-5 mg kg-1) also dose-dependently induced jejunal vasoconstriction. The jejunal vascular resistance returned to control values as the cumulative doses reached 10 and 20 mg kg-1, which corresponded to the maximal increase in jejunal motility. 3. A single intravenous injection of L-NAME (10 mg kg-1) produced a prompt increase in blood pressure, which lasted for at least 50 min. 4. L-NAME (10 mg kg-1) produced a progressive rise in jejunal motility reaching its maximum (47 +/- 6 mmHg) 15 min after the administration, and lasting for 40-50 min. Both the basal lumen pressure and the amplitude of rhythmic contractions increased during this period. 5. L-NAME (10 mg kg-1) produced a triphasic change in jejunal vascular resistance and blood flow measured by timed collection of venous outflow. The blood flow decreased initially (-43% at 5 min), increased (+35%) and returned to control value between 15 and 35 min, then decreased (-35%) 40-50 min post-infusion. Jejunal vascular resistance reflected the blood flow response (+88% at both 5 and 50 min). The time during which the reversal of the vasoconstriction occurred (15-35 min) corresponded to the time of marked increase in motility, and was accompanied by a significant increase in jejunal oxygen uptake (+ 18%).6. The L-NAME-induced increase in motility was prevented by L-arginine (1 g kg-1, i.v.) but not by D-arginine pretreatment. The interim (15-35 min) changes in jejunal blood flow, vascular resistance and oxygen uptake were also prevented by L-arginine pretreatment.7. L-Arginine pretreatment attenuated L-NAME-induced hypertension for 5 min.8. The L-NAME-induced increases in jejunal vascular resistance and motility were inhibited by either local intra-arterial infusion of L-arginine (32 mM local arterial blood concentration) or topical application of 2 MicroM nitroglycerin. Infusion of D-arginine (32 mM local arterial blood concentration) had no such effect.9. The L-NAME-induced increase in blood pressure was not the mechanism by which jejunal motility was increased, because similar increases in blood pressure by mefenamate (10 mg kg-1, i.v.) had no such effect.10. Thus, inhibition of nitric oxide synthesis by L-NAME increased jejunal motility and vascular resistance and the marked increase in motility can abolish or reverse the vasoconstriction. Endogenous nitric oxide may play a role in regulating motility and blood flow in the resting canine jejunum.
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PMID:L-NAME, nitric oxide and jejunal motility, blood flow and oxygen uptake in dogs. 801 97

1. We assessed regional haemodynamic responses to the vasodilator, MgSO4, in the absence and presence of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), in conscious chronically instrumented Long Evans rats (n = 9). 2. MgSO4 (loading dose 220 mumol kg-1 min-1 for 7 min, maintenance dose 56 mumol kg-1 min-1 for 7 min), alone, caused slight bradycardia and hypotension accompanied by reductions in renal and mesenteric flows, but a marked hyperaemic vasodilatation in the hindquarters (flow, delta 54 +/- 6%, vascular conductance, delta 77 +/- 5%). 3. L-NAME (183 nmol kg-1 min-1) caused hypertension (29 +/- 2 mmHg) accompanied by bradycardia (-51 +/- 6 beats min-1) and reductions in flow and vascular conductance in the renal (-18 +/- 4% and -35 +/- 3%, respectively), mesenteric (-35 +/- 3% and -49 +/- 3%, respectively), and hindquarters (-26 +/- 3% and -42 +/- 3%, respectively) vascular beds. In the presence of L-NAME, the hypotensive and bradycardic effects of MgSO4 were still apparent, but its hindquarters hyperaemic vasodilator effect was significantly attenuated. 4. In order to determine if the inhibitory action of L-NAME on the hindquarters hyperaemic vasodilator action of MgSO4 was a non-specific effect, due to the change in baseline conditions caused by L-NAME, we also examined responses to MgSO4 in the presence of endothelin-1 (12.5 pmol kg-1 min-1) or angiotensin II (50 pmol kg-1 min-1). In the presence of either peptide, the overall effects of MgSO4 on hindquarters flow and vascular conductance were unchanged. 5. In a separate experiment (n = 8) we determined that the inhibitory effect of L-NAME on the hyperaemic vasodilator response to MgSO4 was prevented by L-arginine, and also demonstrated that the Beta2-adrenoceptor antagonist, ICI 118551, caused significant inhibition of the hindquarters haemodynamic effects of MgSO4.6. We conclude that the hindquarters haemodynamic effects of MgSO4 in conscious rats involve a substantial L-NAME-sensitive component which depends on activation of Beta2-adrenoceptors, probably asa consequence of adrenal medullary adrenaline release.
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PMID:Effects of NG-nitro-L-arginine methyl ester on regional haemodynamic responses to MgSO4 in conscious rats. 801 14

In up to 60% of women with chronic renal disease an elevation of blood pressure is seen during pregnancy. The pathogenesis of this complication may be related to a diminished synthesis of vasodilatory substances by endothelial cells and to an increased sensitivity to vasopressor hormones such as angiotensin II. Previous experimental studies in rats with early chronic renal disease (adriamycin nephropathy, AN) have shown that this pregnancy-induced hypertension is associated with a lowered synthesis of glomerular PGE2. In the present study the vascular response to vasoactive substances was evaluated. In AN rats the sensitivity to an acute infusion of angiotensin II was augmented, whilst it was blunted in normal pregnant rats. Chronic treatment with the thromboxane-(Tx)-receptor antagonist, daltroban (60 mg/kg/day, p.o.) administered from mid-pregnancy induced a similar reduction in blood pressure in both AN virgin and pregnant rats. This suggests that adriamycin per se may induce vascular damage which may interfere with the normal vascular adaptation to pregnancy. Stimulation of NO synthesis with L-arginine decreased MAP values significantly in PAN rats but did not modify them during normal pregnancy. In additional experimental inhibition of the endothelial-derived relaxing factor (EDRF), nitric oxide (NO) synthesis with NAME from mid-pregnancy significantly increased SBP and MAP in normal rats. By contrast, in PAN rats chronic NAME treatment had no effect. In summary, the development of hypertension in pregnant rats with AN may be associated to endothelial cell dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pregnancy-induced hypertension in rats with early adriamycin nephropathy. 807 19

1. The use of pharmacological inhibitors of nitric oxide (NO) synthesis to treat patients with septic shock is limited by the observation that they cause a fall in cardiac output in some subjects. The aim of this work was to investigate this fall and to test whether it was reversible by subsequent administration of nicardipine, theophylline or the cyclic GMP-selective phosphodiesterase inhibitor, zaprinast (M&B 22948). 2. In pentobarbitone-anaesthetized pigs, haemodynamic indices were measured before and after intravenous administration of NG-nitro-L-arginine methyl ester (L-NAME) in a dose-response protocol (0.2-20 mg kg-1; n = 6) and as a single bolus of 10 mg kg-1 either alone or followed by increasing doses of nicardipine, theophylline or zaprinast (n = 8 in each group). 3. L-NAME caused a dose-dependent rise in systemic vascular resistance and mean systemic arterial pressure and a dose-dependent fall in cardiac output. A single bolus of L-NAME (10 mg kg-1) produced these effects within 15 min. 4. Subsequent administration of nicardipine (0.05-0.2 mg kg-1) caused complete reversal of systemic vasoconstriction and hypertension and in doing so completely restored cardiac output. Theophylline (7.5-10 mg kg-1) partially reversed the rise in systemic vascular resistance and partially restored cardiac output but the effect was small compared to that of nicardipine. Zaprinast (1-5 mg kg-1) had no significant effect on any of these variables. 5. These results suggest that reduced cardiac output following inhibition of NO synthesis is an effect of increased afterload on the heart and is reversible by nicardipine and to a lesser extent by theophylline.These findings may have potential value for those using NO synthase inhibitors to treat patients with septic shock.
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PMID:Comparison of the ability of nicardipine, theophylline and zaprinast to restore cardiovascular haemodynamics following inhibition of nitric oxide synthesis. 807 60

1. The chronic inhibition of nitric oxide synthesis by N omega-nitro-L-arginine-methyl ester (L-NAME) leads to arterial hypertension accompanied by a significant increase in cardiac sympathetic tone and an almost complete abolition of the vagal tone in conscious adult male Wistar rats. The main aim of the present study was to examine the baroreceptor heart rate reflex function in L-NAME-treated rats (N = 10). 2. Spontaneous daily oral intake of L-NAME (1 mg/ml for 6 days) caused marked hypertension and tachycardia (176 +/- 5 mmHg and 418 +/- 16 bpm), when compared to untreated rats (111 +/- 2 mmHg and 354 +/- 8 bpm). 3. Baroreflex gain was determined in conscious freely moving rats by sigmoidal curve fitting analysis using alternate intravenous injections of phenylephrine (0.2-10.0 micrograms/kg) and sodium nitroprusside (0.5-20.0 micrograms/kg) to produce pressor-induced bradycardia and depressor-induced tachycardia, respectively. The baroreflex gain (sensitivity) was significantly enhanced in L-NAME-treated rats compared to control rats (10.9 +/- 2.5 vs 4.5 +/- 0.3 bpm/mmHg, respectively) mainly due to exaggerated reflex bradycardia responses to increases in arterial hypertension. 4. The data indicate that chronic inhibition of nitric oxide synthesis enhances the bradycardic component of the baroreflex function.
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PMID:Baroreceptor reflex function in rats submitted to chronic inhibition of nitric oxide synthesis. 808 3

We studied the effect of endothelium on the flow-induced response of conductance arteries and the resistance arteriolar network in an in situ model of perfused mesenteric artery in normotensive Wistar-Kyoto and spontaneously hypertensive rats. The mesenteric network was perfused with a Tyrode's albumin solution. The diameter of a conductance mesenteric artery was measured using a video camera system, and mesenteric pressure was recorded in a collateral artery. The preparation was perfused at 0.2, 2, and 4 mL/min, and flow-diameter-pressure relations were established (1) under control conditions, (2) during local inhibition of nitric oxide synthesis by topical application of N omega-nitro-L-arginine methyl ester (L-NAME) (1 mmol/L), and (3) after endothelium removal (CO2 drying). In normotensive rats, L-NAME decreased conductance artery diameter by 12 +/- 2% (P < .01) at 0.2 mL/min and 3.3 +/- 1.9% (P < .05) at 2 mL/min. In hypertensive rats, L-NAME did not modify mesenteric diameter. Endothelium removal markedly increased arterial resistance in both strains and decreased conductance artery diameter in normotensive rats (10.3 +/- 3%, P < .05 at 0.2 mL/min and 4.2 +/- 2%, P < .05 at 2 mL/min) but not in hypertensive rats. The present study suggests that the endothelium plays a similar role in the control of mesenteric resistance in both strains and that there is a significant diameter-flow dependency affected by both endothelium removal and inhibition of nitric oxide synthesis in conductance mesenteric arteries from normotensive but not from hypertensive rats.
Hypertension 1994 Oct
PMID:Alterations in flow-dependent vasomotor tone in spontaneously hypertensive rats. 808 14

This study examined the ability of salbutamol (selective beta 2-adrenoceptor agonist) to cause endothelium-dependent relaxation in rat aortic rings and depressor response in conscious rats. Salbutamol (0.01-100 microM) concentration dependently relaxed preconstricted aortic rings. The relaxant response was partially attenuated by either mechanical removal of the endothelium or treatment with NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). In conscious rats, either i.v. infused phenylephrine (5 micrograms/kg per min) or i.v. bolus injected L-NAME (12.8 mg/kg), but not the vehicle, caused similar sustained increases in mean arterial pressure (MAP). I.v. infused salbutamol (2-128 micrograms/kg per min, each dose for 5 min) dose dependently decreased MAP in vehicle-treated rats; the depressor responses were potentiated by hypertension induced by phenylephrine. In contrast, the magnitudes of the depressor response to salbutamol in L-NAME-treated rats were less than those in rats pretreated with phenylephrine or the vehicle. I.v. bolus injections of salbutamol (0.25-16 micrograms/kg) also caused dose-dependent and transient decreases in MAP in vehicle-treated rats. The magnitude but not the duration of the depressor response to salbutamol was less in rats treated with L-NAME, compared to those in rats given phenylephrine or the vehicle. These results suggest that endothelium-derived nitric oxide is partially involved in beta 2-adrenoceptor-mediated vasodilatation.
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PMID:Endothelium-derived nitric oxide partially mediates salbutamol-induced vasodilatations. 811 92

Previous results have shown that the contractile response to norepinephrine (NE) was enhanced in isolated aortae from SHR and normotensive Wistar parathyroidectomized rats. In this work we sought to characterize the contribution of endothelium-derived relaxing factor (EDRF) release to this effect which is not linked to hypertension. Parathyroidectomy (PTX) was performed by surgery on 5 week-old male Wistar rats. Five weeks later intact (E+) and rubbed (E-) aortic rings were mounted in an organ chamber for isometric tension recording. KCl-induced contractions were potentiated in PTX E+ aortae compared to sham operated (SO), (P < 0.05), but not in denuded E- aortae. Similarly NE (1 nM- 10 microM) induced a potentiated contractile response in PTX E+ (P < 0.01), but not in PTX E- rings; nevertheless the sensitivity did not change. After removal of endothelium, the expected enhanced contraction and sensitivity observed in SO rats was not present in PTX. The NO synthase inhibitor L-NAME (20 microM), enhanced sensitivity to NE in SO but not in PTX E+ aortic rings. In addition, hemoglobin (Hb, 10 microM) enhanced NE contraction in SO (P < 0.01) aortic rings, but to a lesser extent in PTX rat aortae. Moreover, in the presence of L-NAME or Hb, SO and PTX aortae displayed a similar contraction. Superoxide dismutase (SOD, 150 U/ml) diminished the NE contraction since NO was protected from degradation but the difference was still present between SO and PTX rat aortae, ruling out the possible implication of superoxide anions in the hyperreactivity of PTX aortae. On the other hand, A23187, which induces EDRF release, reduced the level of NE contraction as expected, but suppressed the PTX enhancing effect and in calcium-free solution the enhancement of contraction after PTX was not observed. These experiments extend to the rat the observations previously obtained in rabbit aorta: extracellular calcium is a major determining factor in NO production. Acetylcholine and A23187 (cumulative doses) produced an endothelium-dependent relaxation which was not significantly modified in NE-pre-contracted PTX aortae compared to SO aortae. L-arginine (100 microM), reversed the L-NAME inhibitory effect and induced an attenuated endothelium-dependent relaxation in PTX vessels (P < 0.01). In conclusion, in rat isolated aortae the enhancing effect of parathyroidectomy on norepinephrine and KCl contractions is due to a diminished endothelial nitric oxide production. This might arise via a decrease of the constitutive NO synthase activity in an extracellular calcium-dependent manner.
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PMID:Characterization of endothelium-derived relaxing factor involvement in the potentiating effect of parathyroidectomy on norepinephrine-induced rat aortic contraction. 818 95

Chronic nitric oxide (NO) inhibition promotes hypertension and ischemic glomerular injury with only minor glomerulosclerosis (GS). We evaluated the effect of superimposed salt overload, which has been shown to aggravate GS in other models. Fifteen days of treatment with the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) promoted marked arterial and glomerular hypertension, hyporeninemia, and slight renal interstitial expansion, but no glomerular injury. Salt overload slightly exacerbated systemic and glomerular hypertension, promoted albuminuria, interstitial expansion, and glomerular ischemia, and paradoxically reversed hyporeninemia. The angiotensin II inhibitor losartan attenuated glomerular and systemic hypertension and prevented renal injury in these rats. Thirty days of treatment with L-NAME resulted in marked hypertension, hyperreninemia, interstitial expansion, and glomerular ischemia. Concomitant salt overload exacerbated hypertension, interstitial expansion, and ischemia and promoted massive albuminuria, GS, and creatinine retention. Losartan attenuated these effects. Sodium overload aggravates the renal and systemic consequences of chronic NO inhibition by mechanisms that may include paradoxical activation of renin secretion. Interstitial expansion and glomerular ischemia, rather than GS, constitute the chief modalities of renal injury in this model.
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PMID:Sodium excess aggravates hypertension and renal parenchymal injury in rats with chronic NO inhibition. 820 52


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