摘要:

Recent investigations have demonstrated that there is a sustained reduction in arterial blood pressure after a single bout of exercise, ie, postexercise hypotension (PEH). The purpose of this discussion is to integrate the available information on this topic and to review studies using sustained stimulation of somatic afferents in experimental rats as a model to study the role of somatic afferents in PEH. PEH occurs in response to several types of large-muscle dynamic exercise (ie, walking, running, leg cycling, and swimming) at submaximal intensities greater than 40% of peak aerobic capacity and exercise durations generally between 20 and 60 minutes. PEH is observed in both normotensive and hypertensive humans and in spontaneously hypertensive rats but is generally greater in magnitude in hypertensive subjects. The maximal exercise-induced reductions in systolic and diastolic arterial blood pressures have been on average 18 to 20 and 7 to 9 mm Hg, respectively, in hypertensive humans and 8 to 10 and 3 to 5 mm Hg, respectively, in normotensive humans. PEH has been reported to persist for 2 to 4 hours under laboratory conditions. Whether PEH is sustained for a prolonged period of time under free-living conditions remains controversial, although the results of one study indicate that PEH can persist for up to 13 hours. Possible mechanisms involved in mediating postexercise and poststimulation reductions in arterial blood pressure include decreased stroke volume and cardiac output; reductions in limb vascular resistance, total peripheral resistance, and muscle sympathetic nerve discharge; group III somatic afferent activation; altered baroreceptor reflex circulatory control; reduced vascular responsiveness to α-adrenergic receptormediated stimulation; and activation of endogenous opioid and serotonergic systems. It appears that the magnitude of PEH in hypertensive subjects is clinically significant; however, more investigation is required to determine if the duration is sufficient under real-life conditions to contribute to the reduction in blood pressure observed with chronic exercise conditioning.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The aim of this study was to determine the phenotype of smooth muscle cells in the arteries of chronically hypertensive animals and to analyze the effects of treatments known to increase the survival of the animal without a clear effect on its hypertensive state. Stroke-prone spontaneously hypertensive rats (SHRSP) kept on a 1% sodium drinking solution were untreated or treated with one of two diuretics, indapamide (3 mg/kg per day) or hydrochlorothiazide (20 mg/kg per day), from 6 to 13 weeks of age. Phenotype was characterized by the immunolabeling of arteries with antibodies raised against a cellular form (EIIIA) of fibronectin, α-smooth muscle actin, and nonmuscle myosin. We demonstrated that phenotypes of smooth muscle cells of the SHRSP differ from those found in Wistar-Kyoto rats. The difference in phenotype is specific for the vessel type: ie, an increased expression of nonmuscle myosin in the aorta and of both EIIIA fibronectin and nonmuscle myosin in the coronary arteries. The two diuretics (1) had no effect on blood pressure, (2) prevented or did not prevent the increase in medial thickness, and (3) prevented changes in both smooth muscle cell phenotype and ischemic tissular lesions. Taken together, the results suggest that in SHRSP the changes in the phenotype of smooth muscle cells and the thickness of arteries are unrelated events. We propose that the maintenance of the contractile phenotype of the arterial smooth muscle cells could be an essential parameter involved in the prevention of the deleterious consequences characteristic of a severe hypertensive state.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We examined the hypothesis that dilatation of the basilar artery in response to activation of ATP-sensitive potassium channels is impaired in stroke-prone spontaneously hypertensive rats (SHRSP). Changes in basilar artery diameter in response to aprikalim, a direct activator of ATP-sensitive potassium channels, were measured in anesthetized SHRSP and normotensive Wistar-Kyoto (WKY) rats through a cranial window. Topical application of aprikalim increased basilar artery diameter in WKY rats. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, abolished aprikalim-induced vasodilatation. Thus, ATP-sensitive potassium channels are functional in the basilar artery of WKY rats in vivo. Aprikalim (10−6mol/L) dilated the basilar artery by 31±5% (mean ± SEM) in WKY rats but only 5±1% in SHRSP. The concentration-response curve to aprikalim in SHRSP was significantly shifted to the right, but the response to the highest concentration of aprikalim (10−55mol/L) was similar in SHRSP and WKY rats. Vasodilatation in response to norepinephrine was also impaired in SHRSP. Dilator responses of the basilar artery to forskolin, a direct activator of adenylate cyclase, and nitroprusside, a direct activator of guanylate cyclase, were normal in SHRSP. The findings suggest that dilatation of the basilar artery in response to direct activation of ATP-sensitive potassium channels is impaired in SHRSP compared with WKY rats in vivo.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We investigated functional changes in aortic preparations of spontaneously hypertensive rats treated in utero and subsequently up to 20 weeks of age with the angiotensin converting enzyme (ACE) inhibitors ramipril (0.01 and 1 mg/kg per day) and perindopril (0.01 mg/kg per day). Early-onset treatment with the high dose of ramipril inhibited aortic ACE activity, prevented the development of hypertension, increased aortic vasodilator responses to acetylcholine (10c to 10−6mol/L), decreased vasoconstrictor responses to norepinephrine (10−8mol/L), and increased aortic cyclic GMP content by 160%. Low-dose ramipril inhibited aortic ACE activity and attenuated the aortic vasoconstrictor response to norepinephrine but had no effect on blood pressure. Low-dose treatment with ramipril and perindopril resulted in a significant increase in aortic cyclic GMP content by 98% and 77%, respectively. Long-term coadministration of the bradykinin B2-receptor antagonist Hoe 140 abolished the ACE inhibitor–induced increase in aortic cyclic GMP. Our data demonstrate that long-term treatment with ACE inhibitors can alter vascular function of compliance vessels independently of the antihypertensive action. The increase in aortic cyclic GMP was due to bradykinin potentiating the action of the ACE inhibitors.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The purpose of this study was to compare the effects of prostaglandin I2on several cardiovascular parameters and to compare the ability of prostaglandin I, to modify angiotensin II–induced changes in these cardiovascular parameters in spontaneously hypertensive versus normotensive rats. Studies were conducted in adult, age-matched, indomethacin-, and captopril-pretreated spontaneously hypertensive and normotensive rats that had been prepared for assessment of arterial blood pressure, cardiac output (thermodilution), and renal and mesenteric blood flows (transit-time flow probes). In both normotensive and hypertensive rats, intravenous infusions of prostaglandin I2(0.003, 0.03, 0.3, 1, 3, and 10 μg/kg Per minute) dose-dependently reduced mean arterial blood pressure, total peripheral resistance, and mesenteric vascular resistance but not renal vascular resistance. Only minor differences were detected between normotensive versus hypertensive rats with regard to the effects of prostaglandin I2on baseline cardiovascular parameters (ie, in the absence of angiotensin II). In both rat strains, an intravenous infusion of angiotensin II (300 ng/kg per minute) increased mean arterial blood pressure, total peripheral resistance, and renal and mesenteric vascular resistances, and these effects of angiotensin II were similar in the two strains in the absence of prostaglandin I2. In both strains, prostaglandin I2inhibited angiotensin II-induced changes in mean arterial blood pressure, total peripheral resistance, and renal and mesenteric vascular resistances. However, in the renal, but not mesenteric, vasculature of hypertensive rats, the ability of prostaglandin I2to attenuate angiotensin II-induced vasoconstriction was strikingly reduced. These results indicate that although in general spontaneously hypertensive rats respond normally to prostaglandin I2, in the kidney of spontaneously hypertensive rats the ability of prostaglandin I2to attenuate angiotensin II-induced vasoconstriction is reduced. This selective renal defect may relate to the pathogenesis of high blood pressure in this genetic model of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Norepinephrine stores in electrically driven guinea pig isolated atria were loaded with [3H] norepinephrine, and norepinephrine release was deduced from the radioactivity efflux. Electrical field stimulation of sympathetic nerve endings was applied during the refractory period of atrial contractions. The stimulation-induced release of norepinephrine was increased by angiotensin II (Ang II) (10−8to 10−6mol/L) in a concentration-dependent manner. The maximum observed effect was a 55% augmentation. The effects of 10−7and 10−6mol/L Ang II were abolished by 10−6and 10−5mol/L of the subtype I Ang II receptor antagonist losartan, respectively. Losartan by itself (10−6mol/L) caused a 14% reduction of norepinephrine release. The subtype 2 Ang II receptor ligand PD 123319 (l−[[4-(dimethylamino)-3- methylphenyl] methyl] −5-(diphenylacetyl)-4,5,6,7-tetrahydro-l/H-imidazo [4,5 -c]pyridine-6-carboxylic acid ditrifluoroacetate) in a concentration of 10−4mol/L had no detectable influence on transmitter release and did not antagonize the effect of Ang II. Angiotensin I (10−6 and 10−5 mol/L) increased norepinephrine release maximally by 23%. This effect was antagonized by 10−5 mol/L losartan and did not appear in the presence of 10−6mol/L of the converting enzyme inhibitor ramiprilat. These results suggest that Ang II increases norepinephrine release by an activation of subtype 1 receptors, whereas angiotensin I is converted to Ang II to become effective.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Brown Norway Katholiek rats, which have very low levels of plasma kininogens, excreted a much smaller amount of kinin in the urine than normal rats of the same strain. The systolic blood pressure of 7-week-old kininogen-deficient rats fed low (0.3%) NaCl diets (131±4 mm Hg, n=12) was not different from that in normal rats. Two percent NaCI diets given from 7 weeks of age for 4 weeks caused rapid increases in blood pressure (167±4 mm Hg,n=12, 9 weeks old) in deficient rats, although the same diets induced no blood pressure increase in normal rats. Urinary excretion of active kallikrein and prokallikrein remained constant in both rat groups throughout NaCl loading. During this period, the deficient rats secreted less urine (9 weeks old,P<.05) and less urinary sodium (11 weeks old,P<.05). Serum levels of sodium in deficient rats were higher (P<.O5) than in normal rats at 9 weeks of age. Intracellular concentrations of sodium in the erythrocytes of deficient rats were higher (P<.05) than in normal rats throughout NaCl loading. Subcutaneous infusion of bovine low molecular weight kininogen with an osmotic pump in NaCI-loaded deficient rats induced a reduction (P<.01) in blood pressure and increases (P<.05) in urine volume and urinary sodium and kinin levels. By contrast, subcutaneous infusion of the bradykinin antagonist Hoe 140 or of aprotinin in NaCl-loaded normal rats induced a hypertensive response. This antagonist treatment reduced urine volume and urinary sodium. These results indicate that the lack of kinin generation observed in the kininogen-deficient rats was related through sodium retention to the hypertensive response to NaCl loading.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The present study investigated whether high salt intake (8%) in Dahl salt-sensitive and salt-resistant rats with and without hypertension produces a heterologous desensitization of cardiac adenylyl cyclase as observed in various types of hypertension and human heart failure. In membranes from Dahl saltsensitive rats on a high-salt diet (8%) basal, isoproterenol-, 5′-guanylylimidodiphosphate-, and forskolinstimulated adenylyl cyclase was reduced compared with the low-salt (0.4%) group and Dahl salt-resistant rats on either 0.4% or 8% sodium chloride. The activity of the catalyst was depressed, and the expression of the immunodetectable inhibitory G proteins Gliαwas increased in Dahl salt-sensitive rats on 8% sodium chloride, whereas the density of β-adrenergic receptors and the activity of the stimulatory G protein Gsαreconstituted into Gsα-deficient S49 cyc−mouse lymphoma cell membranes were unchanged in any condition studied. We conclude that high salt intake in salt-sensitive hypertensive Dahl rats produces hypertension, cardiac hypertrophy, and heterologous desensitization of cardiac adenylyl cyclase. The latter alteration is due to an increase of Giα proteins and a depressed catalyst activity of adenylyl cyclase. The results demonstrate that heterologous adenylyl cyclase desensitization can precede the development of contractile dysfunction in later stages and can occur independently of changes in β-adrenergic receptors.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We studied the effects of a single dose (100 mg orally) and repeated administration (100 mg o.d. for 7 days) FK453, a novel adenosine-1 receptor antagonist, on renal sodium handling and blood pressure in eight patients with essential hypertension. Within 60 minutes after administration of FK453, sodium excretion increased threefold. This occurred in the absence of a change in renal hemodynamics, assessed from inulin and para-aminohippurate clearance, and was accompanied by increased fractional excretion of lithium, phosphate, and uric acid and by increased excretion of calcium and magnesium. Maximal free water clearance data showed an increase in maximal urine flow and distal delivery term and a decrease the diluting segment reabsorption term. FK453 also decreased blood pressure and increased heart rate, but this did not occur until about 3 hours after ingestion, that is, when the natriuresis was already over. The natriuretic effect of FK453 was short-lasting, and continued use of FK453 was in fact accompanied some net sodium retention. Blood pressure on the seventh day before FK4S3 treatment was not different from blood pressure before administration of the first dose of FK453. Again an acute natriuretic response followed, although less than after the first dose. Changes in intrarenal sodium handling parameters, blood pressure, and heart rate were similar to those seen after the first dose. The natriuretic and hypotensive effects of FK453 indicate that adenosine-1 receptor activity plays a role in the regulation of blood pressure and renal sodium handling in patients with essential hypertension. Although these findings are not necessarily specific for this condition, it seems worthwhile to evaluate whether adenosine-1 antagonism can be used as a mode to treat hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Resistance to insulin-induced glucose disposal is associated with hypertension, in accord with recent reports that insulin-induced vasodilation is impaired in men with resistance to insulin-induced glucose disposal. Nevertheless, the mechanism of insulin-induced vasodilation is not known. We wished to determine whether a physiological concentration of insulin inhibits agonist-induced contraction at the level of the individual vascular smooth muscle cell, and if so, how. Dispersed vascular smooth muscle cells from dog femoral artery were grown on collagen gels for 4 to 8 days. Contraction and intracellular Ca2+concentration of individual cells were measured by photomicroscopy and fura 2 epifluorescence microscopy, respectively. Serotonin and angiotensin II contracted cells in a dose-dependent manner. Preincubation of cells for 20 minutes (short-term) or 7 days (long-term) with insulin (40 μU/mL) inhibited serotonin- and angiotensin II–induced contractions by approximately 50%. Insulin (10 μU/mL) acutely inhibited serotonin-induced contraction by 34%. The maximal effect of high extracellular K+–induced contraction was not affected by short-term insulin exposure, but the ED50for extracellular K+–induced contraction was increased from 7.6±2.5 to 16.0±3.9 mmol/L (P<.05). Short-term insulin exposure also attenuated the peak rise of the serotonin-induced intracellular Ca2+transient and increased the rate constant for intracellular Ca2+decline. Verapamil and ouabain completely blocked the attenuation of agonist-induced contraction by short-term insulin exposure, indicating the importance of voltage-operated Ca2+channels and the Na+-K+pump for this effect. We conclude that a physiological insulin concentration inhibits extracellular K+– and agonist-induced contractions at the level of the vascular smooth muscle cell and attenuates the intracellular Ca2+transient in agonist-stimulated cells. Insulin may stimulate Na+-K+pump activity, which hyperpolarizes the cell, thereby decreasing Ca2+influx via voltage-operated channels.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID