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

We designed the present study to clarify whether the intracellular pH change by ammonium chloride influences endothelium-dependent relaxation in thoracic aorta of 9-week-old Sprague-Dawley rats. Intracellular alkalinization with 3 mmol/L ammonium chloride, which did not affect resting vascular tone, attenuated acetylcholine-induced relaxation but not nitroglycerin vasodilation. Acetylcholine relaxation was more inhibited by a shorter duration of treatment. Thus, change in intracellular pH may be important in the effect because the alkalinizing effect of ammonium chloride disappears gradually. In support of this, the proton ionophore nigericin abolished the effect. Also, amiloride shortened the effect of ammonium chloride, suggesting that intracellular pH plays a role: sodium-proton antiport antagonizes the disappearance of ammonium chloride-induced intracellular alkalinization. The synthesis of vasoconstrictor prostaglandins, such as thromboxane A2, may be stimulated during acetylcholine treatment, resulting in the attenuation of acetylcholine relaxation, because the relaxation was abolished by treatment with the phospholipase A2 inhibitor quinacrine, cyclooxygenase inhibitor indomethacin, prostaglandin H2/thromboxane A2 receptor antagonist S1452, and thromboxane A2 synthase inhibitor dazmegrel. Phospholipase A2 may contribute to the effect of intracellular alkalinization, which is compatible with the fact that the optimal pH of phospholipase A2 is neutral to alkaline. In addition, superoxide dismutase attenuated the effect of ammonium chloride. In conclusion, intracellular alkalinization by ammonium chloride attenuated acetylcholine-induced relaxation, possibly through the interrelated production of both thromboxane A2 and superoxide radicals.
Hypertension 1994 Aug
PMID:Inhibitory effect of ammonium chloride on acetylcholine-induced relaxation. 803 43

The mechanism of hypoxic moderation of systemic systolic blood pressure was investigated in spontaneously hypertensive rats (SHR). Male SHR rats were divided into hypoxic (H, 5000 m for 15 d) and normoxic (N) groups. The systemic blood pressure of SHR-H (24.9 +/- 1.2 kPa) was found to be 3 kPa lower than that in SHR-N (27.0 +/- 1.3 kPa) (P < 0.05). This protective effect may have been related to the adaptive changes in vascular reactivity which manifested as an increase in the relaxation response of the aorta to ACh (P < 0.01) and a drop in its contraction in response to 5-HT (P < 0.05) following hypoxic exposure. The hypoxic moderating effect against the development of systemic hypertension may have also been related to the increased plasma levels of ANP observed.
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PMID:The hypoxic moderation of systemic hypertension in spontaneously hypertensive rats. 814 25

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

To examine the effects of L-arginine (L-Arg) on endothelial function, we administered 0.5 g/L L-Arg in drinking water to deoxycorticosterone acetate (DOCA)-salt rats for 8 weeks and then measured nitric oxide (NO) release from isolated kidneys using a newly developed real-time chemiluminescence method. Renal pathology was also analyzed. Acetylcholine caused much smaller declines in renal perfusion pressure (10(-7) mol/L acetylcholine: -24 +/- 2% [SEM] versus -50 +/- 2%, P < .001) and NO release in DOCA-salt rats (+3 +/- 1 versus +33 +/- 3 fmol/min per gram kidney weight, P < .001) compared with control rats. L-Arg did not influence the time course of systolic blood pressure elevation in DOCA-salt rats (211 +/- 5 versus 208 +/- 6 mmHg, DOCA versus L-Arg/DOCA, P = NS). However, oral administration of L-Arg improved acetylcholine-induced declines in renal perfusion pressure (10(-7) mol/L acetylcholine: L-Arg/DOCA, -39 +/- 3%, P < .01 versus DOCA). This change was associated with an increase in NO release by acetylcholine (10(-7) mol/L acetylcholine: L-Arg/DOCA, +10 +/- 1 fmol/min per gram kidney weight, P < .05 versus DOCA). However, morphological changes in renal vessels and glomeruli were similar between DOCA and L-Arg/DOCA rats. These results suggest that L-Arg administration partially reverses renal endothelial function with respect to vasorelaxation and NO release independent of blood pressure changes, indicating that hypertensive vessels seem to be depleted of L-Arg and/or have defects in the availability of L-Arg for NO synthesis.
Hypertension 1994 Jun
PMID:Long-term administration of L-arginine improves nitric oxide release from kidney in deoxycorticosterone acetate-salt hypertensive rats. 820 73

This study determined to what extent active and passive wall tensions increase in in vivo intestinal arterioles of 13- to 15-week-old and 25- to 27-week-old spontaneously hypertensive rats (SHR) to maintain normal or smaller arteriolar diameters during microvascular hypertension. Acetylcholine and nitroprusside were used to determine whether vascular muscle relaxation to endothelium-derived relaxing factor or cyclic GMP is impaired. Large arterioles of hypertensive rats have passive tension-circumference relations that are steeper and shifted to the left compared with those of age-matched controls; passive resistance to distension limits vasodilation in hypertensive rats except at their naturally elevated arteriolar pressure. Passive tension contributes approximately 30% of the total resting tension in arterioles of hypertensive and normotensive rats because a greater passive tension occurs at the 20% to 25% constricted resting diameter in hypertensive rats. Absolute and relative changes in the diameter of SHR arterioles during acetylcholine and nitroprusside application were equal to or greater than those in Wistar-Kyoto rats. However, reduction in active tension was suppressed in older SHR and remained approximately 50% higher than that found in older Wistar-Kyoto rats during drug application. Vasoconstriction and increased passive resistance to distension of the arteriolar wall diminish the active tension required to maintain normal or smaller resting diameters against microvascular hypertension. However, the elevated microvascular pressure in hypertensive rats is required to allow near-normal dilation to compensate for their increased passive resistance to stretch and decreased ability to relax active tension through cyclic GMP mechanisms.
Hypertension 1994 Jun
PMID:Active and passive arteriolar regulation in spontaneously hypertensive rats. 820 74

Vasoconstriction and hypertension are major side effects of cyclosporine therapy. The mechanism or mechanisms responsible for the vascular effects of cyclosporine are unclear. The vascular effects of cyclosporine may arise as a consequence of endothelial dysfunction induced by the agent. To test this possibility, we compared in vessels prepared in myographs endothelium-mediated relaxations of mesenteric resistance arteries of Wistar-Kyoto rats treated for 21 to 28 days with subcutaneous injections of cyclosporine (25 mg/kg per day), or vehicle. Endothelium-dependent relaxations in response to acetylcholine were impaired in arteries from cyclosporine-treated rats; the concentrations of acetylcholine required to produce 50% relaxation of norepinephrine activation (pD2) were 31.6 +/- 0.1 versus 5 +/- 0.1 nmol/L in control arteries (P < .05). Nitro-L-arginine produced comparable 10-fold decreases in sensitivity to acetylcholine in arteries from both rat groups, indicating that the relaxations were mediated by endothelium-derived nitric oxide. Acetylcholine-induced relaxations in cyclosporine-treated arteries were normalized by pretreatment of the arteries with superoxide dismutase (150 IU/mL; pD2, 3.6 +/- 0.1; P < .05); superoxide dismutase had no effect on relaxations in control arteries. SQ 29,548, an inhibitor of prostaglandin H2/thromboxane A2 receptors; H-7, an inhibitor of protein kinase C; and indomethacin did not alter relaxations in response to acetylcholine in either group of arteries. Cyclosporine-treated arteries were more sensitive than control arteries to nitroprusside, an agent that induces relaxation via nitric oxide (pD2, 1.3 and 6.2 mumol/L, respectively; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jun
PMID:Cyclosporine produces endothelial dysfunction by increased production of superoxide. 820 35

We investigated the effects of inhibition of both nitric oxide (NO) synthesis and angiotensin converting enzyme (ACE) on agonist-induced relaxations in the coronary system. Chronically instrumented conscious dogs (n = 4) 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). Intracoronary infusions of acetylcholine, adenosine and bradykinin were performed after intracoronary pretreatment of either vehicle, L-NAME (6 mg.kg-1), captopril (1 mg.kg-1) or both L-NAME+captopril. Acetylcholine bradykinin and adenosine caused dose-dependent increases in CBF and LCX. HR increased concomitantly. Captopril potentiated the vasodilating effects of bradykinin and acetylcholine on LCX and CBF significantly (P < or = 0.05) and those of adenosine slightly. L-NAME caused vasoconstriction, hypertension and bradycardia. The effects of acetylcholine on CBF were abolished during L-NAME treatment while bradykinin and adenosine responses were markedly reduced. When captopril and L-NAME were given simultaneously, the vasodilator responses to bradykinin but not to acetylcholine or adenosine were partially restored (P < or = 0.05). We conclude that in vivo, (a) adenosine possibly elicits endothelium-dependent dilation; (b) adenosine and bradykinin act in part independently of the L-arginine/NO pathway; (c) vasodilation to acetylcholine is potentiated by acute ACE inhibition via NO-dependent mechanisms.
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PMID:Coronary vasodilation to acetylcholine, adenosine and bradykinin in dogs: effects of inhibition of NO-synthesis and captopril. 829 69

Vascular relaxations are impaired in adult spontaneously hypertensive rats (SHRs) because of increased production of an endothelium-derived, cyclooxygenase-dependent contractile factor or factors. To test the hypothesis that alterations in endothelial function precede and contribute to the development of overt hypertension in SHRs, we compared in myographs endothelium-mediated relaxations of mesenteric resistance arteries from 4-week-old SHRs and Wistar-Kyoto (WKY) rats. Acetylcholine (10(-9) to 10(-4) M) induced comparable relaxations in SHR and WKY arteries precontracted (ED50) with norepinephrine. In arteries obtained from SHRs but not from WKY rats, relaxations were replaced by contractile responses with higher concentrations of acetylcholine (10(-6) to 10(-5) M). The contractile responses were endothelium dependent, were augmented by nitro L-arginine (10(-4) M), and were prevented by pretreatment with indomethacin (10(-5) M) or 3-amino-1,2,4-triazole (10(-3) M), an inhibitor of superoxide anion production via the cyclooxygenase pathway. Inhibition of thromboxane synthetase (CGS-13080, 5 x 10(-5) M) and antagonism of prostaglandin H2/thromboxane A2 receptors (SQ-29,548, 5 x 10(-5) M) failed to block the contractile response to acetylcholine in SHR arteries. Acetylcholine-mediated relaxations were significantly impaired in mesenteric arteries from 16-week-old SHRs but not from WKY rats. Endothelium-independent relaxations produced by sodium nitroprusside and contractile responses to norepinephrine and endothelin were comparable in arteries from SHRs and WKY rats of all ages. In summary, endothelium-dependent relaxations of mesenteric arteries from "prehypertensive" SHR rats were impaired by the production of a contractile factor (or factors) that appears to be superoxide anions.
Hypertension 1993 Mar
PMID:Endothelium-derived contracting factors in resistance arteries of young spontaneously hypertensive rats before development of overt hypertension. 838 99

The influence of diabetes on the function of vascular endothelium was examined with respect to the role of nitric oxide (NO) in the regulation of blood pressure (BP) in vivo, the vascular relaxation, and levels of cAMP and cGMP in the effluent of the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats. An intravenous injection of 100 mg/kg N omega-nitro-L-arginine methylester (L-NAME) caused hypertension in both diabetic rats and controls. However, the degree of hypertension in the diabetic rats was significantly lower than that in the controls. Acetylcholine (ACh)-induced vasorelaxation of the perfused mesenteric arterial bed decreased in diabetic rats. At the same time, the levels of cAMP and cGMP in the effluent of the diabetic rats were also lower than in the controls. These data indicate that NO formation is involved in the regulation of BP in rats, and is decreased in diabetic rats, due to an impairment of the vascular endothelium, including the endothelium of resistance vessels.
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PMID:Changes in endothelium-dependent relaxation and levels of cyclic nucleotides in the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats. 839 May 94

We examined whether coronary risk factors and atherosclerotic lesions in the study artery were associated with impaired endothelium-dependent dilation of coronary resistance arteries. Acetylcholine (ACH) at graded doses (1, 3, 10 and 30 micrograms/min) and papaverine (10 mg) were selectively infused into the left anterior descending coronary artery of 28 patients, in whom the study artery was angiographically normal (n = 16) or with mild stenosis < or = 40% (n = 12). Coronary blood flow (CBF) was estimated from the product of mean CBF velocity measured by an intracoronary Doppler catheter and the arterial cross-sectional area of the study artery determined by quantitative arteriography. ACH increased CBF in a dose-dependent manner. However, the maximum CBF response to ACH varied widely among patients (from 50% to 660%). By multivariate analysis, the presence of atherosclerotic lesions in the study artery was an independent predictor for impaired CBF response to ACH (P < 0.01). Hypertension (P < 0.001), hypercholesterolemia (r = -0.52, P < 0.005), age > or = 50 yr (P < 0.01) and total number of coronary risk factors (r = -0.62, P < 0.001) were associated with the impaired increase in CBF with ACH by univariate analysis. The percent increase in CBF evoked with papaverine did not correlate with these risk factors. The results suggest that mild atherosclerotic lesions in the study artery and coronary risk factors are accompanied by impaired endothelium-dependent dilation of coronary resistance arteries evoked with ACH. Endothelial dysfunction of coronary resistance arteries may result in altered regulation of myocardial perfusion in patients with mild coronary atherosclerosis and coronary risk factors.
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PMID:Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions. 842 26


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