摘要:

Endothelin-1 contracts vascular smooth muscle and inhibits release of neurotransmitter from adrenergic and cholinergic neurons. Experiments were designed to investigate the interaction of these mechanisms in a blood vessel that receives both adrenergic and cholinergic innervation. Rings cut from canine left anterior descending coronary arteries were suspended in organ chambers for the measurement of isometric force. In some rings, the endothelium was removed. Endothelin-1 caused concentrationdependent increases in tension in all rings. During electrical stimulation (1 Hz, 9 V, 2 msec), the contractions to endothelin-1 were reduced significantly. In rings without endothelium, this decrease was greater in the presence of atropine (10−6M) and was eliminated by a combination of phentolamine (10−5M) and propranolol (5×10−6M). Contractions to endothelin-1 during electrical stimulation in rings with endothelium were significantly less than those without endothelium. This difference was eliminated by atropine andNG-monomethyl L-arginine (10−4M). The presynaptic effects of endothelin-1 were studied by measurement of tritium-labeled norepinephrine. Phasic electrical stimulation induced release of norepinephrine; this was inhibited by endothelin-1 at high concentrations (4×10−7M) in the presence of atropine. These results suggest that the major effect of endothelin-1 is postsynaptic in canine coronary arteries. However, contractions to endothelin-1 may be modulated by the level of sympathetic and parasympathetic tone. In situations in which innervation to the coronary arteries is altered, for example, in hearts used for transplantation, the contractile effects of endothelin-1 would prevail.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

It has been shown that alcohol administration causes baroreceptor reflex inhibition. The site of action of alcohol could reside anywhere within the baroreceptor reflex arc. Therefore, the goal of this study was to determine the effects of acute administration of alcohol on carotid sinus baroreceptor discharge characteristics. In pentobarbital-anesthetized dogs, the carotid sinus was isolated and perfused. Single unit baroreceptor discharge was recorded from the carotid sinus nerve along with carotid sinus diameter using sonomicrometry. Carotid sinus pressure-baroreceptor discharge and carotid sinus pressurediameter curves were constructed. Perfusion of the carotid sinus with alcohol (100 mmol/L) significantly decreased the pressure threshold from 91.1±2.8 to 86.4±2.9 mm Hg (p<0.05) and increased the peak discharge rate from 45.8±3.4 to 52.8±3.6 spikes per second (p<0.01). The same phenomenon was seen during perfusion of the carotid sinus with acetaldehyde (2.5 mmol/L) but was not seen during perfusion with acetate (2.5 mmol/L). During perfusion of the carotid sinus with alcohol, the carotid sinus pressure-carotid sinus diameter relation did not change. The baroreceptor sensitization induced by alcohol is not an endothelium-dependent mechanism, because endothelial denudation did not block this alcohol-induced effect. Measurement of the duration of postexcitatory depression of carotid sinus baroreceptors, which is related to Na+,K+-ATPase activity, showed that perfusion of the carotid sinus with alcohol or acetaldehyde significantly reduced the duration of postexcitatory depression, indicating that the alcohol- and acetaldehyde-induced effect on baroreceptor discharge is most likely mediated by an inhibition of Na+,K+-ATPase. These data strongly suggest that the inhibition of the baroreceptor reflex after acute alcohol administration does not reside in the afferent limb of the baroreceptor reflex arc.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The purpose of this study was to elucidate the role of endogenous angiotensin II in mediating the renovascular effects of renal adrenergic stimulation. Six conscious dogs instrumented for monitoring of renal blood flow were subjected to step increases every 10 minutes in the rate of norepinephrine infusion into the renal artery. Under control conditions, infusion of norepinephrine (10–40 ng/min per milliliter per minute of control renal blood flow) increased plasma renin activity and decreased renal blood flow progressively by ∼10–75%. When increments in angiotensin II during norepinephrine infusion were abolished by fixing plasma levels of angiotensin II at either normal or high concentrations by chronic infusion of captopril plus angiotensin II, renal blood flow responses to adrenergic stimulation were greatly attenuated at rates of norepinephrine infusion that decreased renal blood flow up to ∼40% under control conditions. Thus, acutely generated angiotensin II appeared to contribute to the renovascular effects of norepinephrine. However, when endogenous levels of angiotensin II were suppressed to low levels by chronic infusion of captopril alone, norepinephrine induced severe renal ischemia at much lower rates of infusion than occurred when the renin-angiotensin system was intact. Since this enhanced sensitivity to norepinephrine did not occur during chronic captopril infusion when angiotensin II was given simultaneously at rates that restored mean arterial pressure to normotensive levels or higher, low arterial pressure during chronic captopril administration may predispose the kidneys to excessive renal vasoconstriction during renal adrenergic stimulation.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Losartan is an orally active, nonpeptide angiotensin II (Ang II) (site-1) receptor antagonist. We conducted a multiple-dose study in healthy male volunteers to investigate the tolerability, blood pressure effects, and changes in plasma renin activity (PRA) and plasma Ang II concentration associated with once-daily administration of 100 mg losartan for a week. Subjects were studied on a standardized sodium diet (24-hour urinary sodium excretion, 98±37 [SD] mEq per 24 hours on the placebo run-in day). Measurements of blood pressure, heart rate, PRA, Ang II, and aldosterone were taken during a placebo run-in day and after single and multiple (7 days) daily doses of losartan (100 mg,n=10) or placebo (n=4). Ang II was measured specifically by high performance liquid chromatography coupled with radioimmunoassay. In subjects given losartan, respective decreases (systolic/diastolic) from run-in in supine blood pressure 6 hours after dosing were (mean±SD), compared with the placebo run-in day, first dose: −8.8±9.6/−6.8±5.0, last dose: −11.6±8.9/−7.0±4.8 mm Hg (p<0.05 for all changes). At this 6-hour time point, corresponding increases from run-in in PRA were from 1.2±0.6 to 12.0±6.3 (first dose) and 9.6±4.9 (last dose) ng angiotensin I per milliliter per hour and in Ang II were from 4.3±1.7 to 72.4±33.3 and 45.7±14.1 pg/mL. All changes in PRA and Ang II were statistically significant within the losartan-treated group, and the biochemical changes were significantly greater than those in the placebo-treated group. The increment in Ang II was less after the last dose than after the first (p<0.05). The drug was well tolerated by all subjects. These data indicate that, under the conditions of this study, losartan administration (100 mg/day for eight doses over 9 days) results in treatment-related decreases in blood pressure and increases in PRA and Ang II octapeptide.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We report on five 6-month experiments during which five colonies of four male and four female rats were exposed to psychosocial stress. Monthly blood pressure measurements by a tail-cuff method showed a modest (10 mm Hg) increase in two studies using Sprague-Dawley rats. In two further studies using the more aggressive Long-Evans strain, terminal direct carotid arterial pressures were taken as well, and in one study the differences exceeded 20 mm Hg. A fifth study used the Wistar-Kyoto, hyperactive (WKHA) strain developed by Hendley, and no differences were observed. Heart and adrenal weights; adrenal catecholamine synthetic enzymes; and heart, aortic, and kidney histology were measured and showed significant changes, which for the most part paralleled blood pressure changes. Social instability and the associated blood pressure changes were made more severe by periodic mixing of males from different colonies. This had no effect on the peaceable WKHA rats, some effect on the Sprague-Dawley rats, and a severe effect on the Long-Evans rats. The WKHA rats failed to show blood pressure changes despite stress-induced increases in heart and adrenal weights. Thus, different types of psychosocial stress and different genetics combine to induce a variety of neuroendocrine changes, not all of which necessarily lead to increased blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The present study was designed to investigate the development of blood pressure and renal sodium handling in recipients of renal grafts from adult stroke-prone spontaneously hypertensive rats (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and borderline hypertensive F1hybrids bred from SHRSP and WKY rats. Unilaterally nephrectomized F1hybrids served as renal graft recipients. The second native kidney was removed 7 days after transplantation. Starting on the day of transplantation, renal graft recipients were put on a standard diet for 7 days followed by a low salt diet (0.18% salt) for 10 days and a high salt diet (1.8% salt) for another 14 days. In recipients of a renal graft from SHRSP donors, systolic blood pressure rose progressively from 140±4 mm Hg before to 190±7 mm Hg 4 weeks after transplantation. In contrast, in recipients of a renal graft from WKY rat donors, blood pressure fell during the same time from 139±7 mm Hg to 120±4 mm Hg. Blood pressure did not change significantly in recipients of a renal graft from F1hybrid donors (132±4 versus 138±7 mm Hg). With transition from a low salt to high salt diet, all rats exhibited renal sodium retention. The accumulating amount of sodium retained by the renal graft was significantly higher in recipients of an SHRSP kidney than in recipients of a WKY rat kidney at all days on the high salt diet. It was also higher in recipients of an SHRSP kidney versus recipients of an F1hybrid kidney on days 8 through 14 on the high salt diet and in recipients of an F1hybrid kidney versus recipients of a WKY rat kidney on days 1 through 5 on the high salt diet. On the low salt diet, urinary aldosterone excretion was lower in recipients of an SHRSP kidney compared with recipients of a WKY rat kidney. On the high salt diet, it was similar in both groups. Urinary corticosterone excretion was similar in both groups on the low salt diet and increased significantly on the high salt diet in recipients of an SHRSP kidney but not in recipients of a WKY rat kidney. At the end of the protocol, glomerular filtration rate, renal plasma flow, plasma sodium concentration, and fractional sodium excretion were not significantly different among groups. These results confirm our previous finding that recipients of a renal graft from SHRSP donors developed posttransplantation hypertension, whereas blood pressure actually decreased in recipients of a renal graft from WKY rat donors. In addition, the data demonstrate that posttransplantation hypertension in recipients of an SHRSP kidney is associated with increased renal sodium retention.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Prior studies describe deficiencies of T-cell-mediated immunity in the spontaneously hypertensive rat (SHR) strain of Okamoto and Aoki. This report describes an alteration of humoral immunity: elevation of the plasma concentration of immunoglobulin (Ig) A and of circulating IgA autoantibodies to single-stranded DNA, double-stranded DNA, and thyroglobulin. The increased plasma IgA levels are evident in prehypertensive SHR, hence not secondary to the hypertension, and they result mainly from increments in polymeric IgA. Plasma IgA content also varied concordantly with the level of systolic blood pressure as influenced by age (older>younger) and gender (male>female) in both the SHR and control Wistar-Kyoto rat strains. Strain differences in plasma IgG or IgM were not observed. Studies of peripheral blood lymphocytes indicate that increased production of IgA is one mechanism for the increment in plasma content. The number of blood lymphocytes capable of producing IgA in vitro in response to the mitogen lipopolysaccharide is increased in SHR. When cultured in the absence or presence of lipopolysaccharide, peripheral blood lymphocytes of SHR secrete more IgA in vitro than do cells of the control strain. No significant strain differences in biliary or renal excretion of IgA were observed. The observed alterations of IgA in the SHR either are causative factors in the development of the hypertension or are the products of an epiphenomenon in which IgA and blood pressure are affected separately, but in parallel, by causative factors related to rat strain, age, and gender.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We investigated the hypothesis that stimulation of metabotropic excitatory amino acid receptors in the ventrolateral medulla evokes cardiovascular responses. Thus, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], a selective agonist of metabotropic excitatory amino acid receptors, was microinjected into the rostral or caudal ventrolateral medulla of halothane-anesthetized Sprague-Dawley rats. Microinjections of (1S,3R)-ACPD (100 pmol-1 nmol) into the rostral ventrolateral medulla produced dose-dependent increases in mean arterial pressure (+20±4 mm Hg by 100 praol and +35±2 mm Hg by 1 nmol,p<0.01 versus artificial cerebrospinal fluid) and integrated splanchnic sympathetic nerve activity (+17±3% and +46±4%, respectively,p<0.01), whereas (1S,3R)-ACPD microinjected into the caudal ventrolateral medulla decreased mean arterial pressure (−28±2 mm Hg by 100 pmol and −48±6 mm Hg by 1 nmol,p<0.01 versus artificial cerebrospinal fluid) and splanchnic sympathetic nerve activity (−24±4% and −49±5%,p<0.01). The blockade of ionotropic excitatory amino acid receptors by the combined injection of 2-amino-7-phosphonoheptanoic acid (200 pmol) and 6,7-dinitroquinoxaline-2,3- dione (200 pmol), which effectively blocked the responses elicited by eitherN-methyl-D-aspartate (20 pmol) or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (5 pmol), failed to affect the responses evoked by either (1S,3R)-ACPD (100 pmol) or L-glutamate (2 nmol) microinjected in the rostral and caudal ventrolateral medulla. These results suggest that metabotropic receptors are present and mediate cardiovascular responses evoked by L-glutamate injections into the rostral and caudal ventrolateral medulla.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID