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

摘要:

This study aimed to determine the mechanism of hypertension associated with nitric oxide synthase inhibition. Intravenous injections ofNG-nitro-L-arginine, a nitric oxide synthase inhibitor, produced a sustained increase in systemic blood pressure and a decrease in heart rate in anesthetized dogs, whereasNG-nitro-D-arginine had no effect. L-Arginine reversed the pressor response.NG-Nitro-L-arginine-induced hypertension was markedly attenuated or abolished by treatment with hexamethonium; this inhibition was still observed when the blood pressure fall caused by the ganglionic blocking agent was compensated by continuous infusion of angiotensin II. In dogs treated with phentolamine in a dose sufficient to lower blood pressure to the level similar to that elicited by hexamethonium and to suppress the pressor response to norepinephrine, the hypertensive effect ofNG-nitro-L-arginine was not attenuated. We conclude that hypertension caused by the nitric oxide synthase inhibitor is associated with an elimination of nitroxidergic neural function rather than an impairment of the basal release of nitric oxide from the endothelium.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We designed experiments to determine the role of endothelium-derived contracting factor or factors in the response to endothelin-1 and endothelin-3 in the aorta of normotensive and hypertensive rats. Rings of thoracic aortas, with and without endothelium, from normotensive and spontaneously hypertensive rats were suspended in organ chambers for recording of isometric tension in the presence of nitro-L-arginine, an inhibitor of nitric oxide synthase. The removal of endothelium decreased the contractions evoked by both endothelins in the aorta of spontaneously hypertensive but not of normotensive rats. Indomethacin (inhibitor of cyclooxygenase), dazoxiben (inhibitor of thromboxane synthase), and SQ-29,548 (antagonist of thromboxane A2receptors) reduced, in aortic rings of spontaneously hypertensive rats, the contractions to endothelins in rings with but not in those without endothelium, whereas their effect was not endothelium-dependent in tissues of normotensive rats. BQ-123, a selective endothelin-A receptor antagonist, shifted the concentration-response curve to endothelin-1 to the right in a concentrationdependent manner and abolished the endothelium-dependent component of the contractions evoked by the peptide. The presence of the endothelium increased the basal and endothelin-stimulated release of thromboxane B2, the stable metabolite of thromboxane A2, in aortas of spontaneously hypertensive rats but not in those of normotensive rats. These data suggest that endothelium-derived thromboxane A2contributes to contractions evoked by endothelin-1 and endothelin-3 in the aorta of the spontaneously hypertensive rat but not in that of the normotensive rat. Both the receptors on the endothelial cells (mediating the release of thromboxane A2) and those on vascular smooth muscle belong to the endothelin-A subtype.

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

摘要:

The effect of changing extracellular calcium and sodium concentrations on flow, acetylcholine, and papaverine vasodilation and also on norepinephrine contraction was studied in a segment of a resistance branch of the rabbit central ear artery mounted in a myograph. Decreases in calcium to 80% of the normal physiological saline solution concentration (1.6 mM) reduced both flow- and acetylcholine-induced dilation. Increases of calcium to 120%, 140%, and 200% of normal decreased flow dilation responses, but not those to acetylcholine and papaverine. Thus, the optimum calcium concentration for flow dilation lies within the range of 1.4–1.9 mM. The concomitant proportionate reduction of sodium and calcium offsets the reduction in flow dilation that occurred with reduction in calcium alone. This was true whether sodium and calcium were reduced simultaneously or whether the effect of lowered sodium and then that of lowered sodium and calcium was studied. Emphasizing the uniqueness of this interaction between sodium and calcium are the observations that the depression of acetylcholine dilation by calcium reduction was not influenced by a concurrent reduction in sodium and that the depression of flow dilation caused by sodium reduction is increased by calcium increase, which by itself depresses flow dilation. None of these changes in sodium and calcium alters the responses of the artery segment to papaverine or norepinephrine. We propose that these interactions of sodium and calcium in relation to flow dilation may reflect the binding properties for sodium and calcium of a proposed flow sensor, the glycosaminoglycan polyanions. These results raise the possibility that vascular tone may be influenced not only by the absolute but by the relative concentrations of sodium and calcium.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The effects of dietary supplementation with marine oils on vascular reactivity in human forearm resistance arteries were studied. Healthy male adults (six to nine subjects per group) were given either maxEPA capsules (content: eicosapentaenoic acid, 0.178 g/g; docosahexaenoic acid, 0.116 g/g) at doses of 20, 10, or 5 g/day or placebo capsules at 20 g/day for 28 days. Capsule compliance was confirmed by measurement of platelet membrane incorporation of n-3 fatty acids. Blood pressure was not affected by either maxEPA or placebo. The influence of treatment interventions on forearm vasoconstrictive responses to local infusions of angiotensin II and norepinephrine was examined using venous occlusion plethysmography before and after treatment. Responses to both agonists were significantly suppressed by 20 g/day maxEPA (slopes before and after maxEPA, respectively: angiotensin II, 3.34 and 0.89; norepinephrine, 0.91 and 0.41). When analyzed as difference in area under the dose–response curves, the suppressive effects of maxEPA were clearly dose dependent (angiotensin II: 20 g area reduced by 72%, 10 g by 67%, 5 g by 33%). Similarly, responses to norepinephrine were dose-dependently suppressed by maxEPA (20 g area reduced by 61%, 10 g by 63%, and 5 g by 33%). Placebo had no effect on the responses to either constrictor. The responses to both agonists returned to preoil levels after 2 months' discontinuation of 20 g/day maxEPA. We conclude that the suppressive effects of marine oils on vascular reactivity may, in part, contribute to their cardioprotective influence in humans.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Angiotensin II, a potent vasoconstrictor and known growth factor for vascular smooth muscle cells, has been implicated in the development of glomerulosclerosis. Because mesangial cell growth plays a critical role in the glomerulosclerotic process, the objective of this study was to determine the direct effect of long-term (48-hour) angiotensin II treatment on the growth of cultured murine mesangial cells. Subconfluent, quiescent adult murine mesangial cells were treated for 48 hours with media containing angiotensin II with and without its specific inhibitor losartan. In comparison to cells treated with serum-free medium, cells treated with serum plus insulin demonstrated a significant increase in cell number (1.93±0.1 times control,p<0.05), [3H]thymidine incorporation per 105cells (2.29±0.12 times control,p<0.05), [3H]leucine incorporation per 105cells (1.81 ±0.18 times control,p<0.05), and total protein content per 105cells (1.65±0.07 times control,p<0.05). In contrast, cells treated with angiotensin II (10−6M) had no significant increase in cell number (0.84±0.01 times control) or [3H]thymidine incorporation per 105cells (1.23±0.12 times control) but demonstrated a significant increase in [3H]leucine incorporation per 105cells (1.61 ±0.09 times control) and total protein content per 105 cells (1.38±0.04 times control). Pretreatment with losartan blocked 56% of the angiotensin II-induced increase in [3H]leucine incorporation and 84% of the angiotensin II-induced increase in total protein content. There was a 7% increase in size in angiotensin II-treated cells and an 18% increase in size in serum plus insulin-treated cells, as demonstrated by fluorescence-activated cell sorting. Cells treated with serum-free medium plus insulin also showed significant increases in tritiated leucine incorporation and total protein content, but there was also an increase in tritiated thymidine incorporation without an increase in cell number. The addition of angiotensin II to insulin did not potentiate the effect of insulin. These results indicate that long-term angiotensin II administration caused hypertrophy without hyperplasia in quiescent, subconfluent cultured adult murine mesangial cells. Blockade of the subtype 1 angiotensin II receptor with losartan partially blocked the hypertrophic effect of angiotensin II. Insulin alone was also a hypertrophic factor for mesangial cells and, in addition, stimulated DNA synthesis. The effects of angiotensin II and insulin were not additive.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Renin secretion responds rapidly to a variety of stimuli; however, reported changes in renal renin messenger RNA (mRNA) levels in vivo have been observed only after prolonged stimulation. Studies were designed to test whether rapid changes in renin mRNA levels can be produced in vivo. In the first series, Sprague-Dawley rats received furosemide (10 mg/kg) intraperitoneally and a low sodium diet (0.05% sodium); renin secretion was significantly stimulated at 8 or 16 hours after treatment, but renin mRNA levels did not change. In a second series, rats were pretreated with deoxycorticosterone acetate (200 mg/kg) and saline drinking water for 3 days and then killed 0, 2, 4, 8, or 48 hours after furosemide administration. The renin mRNA level was unchanged at 2 hours but was stimulated twofold at 4 and 8 hours and threefold at 48 hours. In additional animals, the response of renin mRNA 4 hours after furosemide was found not to be potentiated by the converting enzyme inhibitor quinapril (5 mg/kg). The results demonstrate that with acute stimulation, renin mRNA levels lag 2–4 hours behind the change in plasma renin levels.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Some evidence suggests that RNA complementary to the messenger RNA encoding a peptide hormone encodes a complementary peptide that binds the original peptide hormone. The objective of this investigation was to assess in vivo the ability of complementary angiotensin II (II Ang) peptides to block the biological effects of angiotensin II (Ang II). Increasing concentrations of rat or human II Ang were preincubated with Ang II for 2 hours, and this solution was then infused intra-arterially into the superior mesenteric artery. Human, but not rat, II Ang dose-dependently inhibited Ang II–induced mesenteric vasoconstriction. The in vivo inhibitory potencies of human II Ang and [Sar1,Ile8] Ang II, with respect to inhibition of the pressor response to Ang II, were compared by infusing intravenously increasing doses of each blocker and determining their effects on a fixed intravenous dose of Ang II. Although human II Ang could abolish the pressor response to Ang I I, [Sar1,Ile8] Ang II was approximately 100 times more potent in this regard. A fixed dose of human II Ang (150 μg/min i.v.) inhibited the effects of increasing doses of Ang II on mesenteric vascular resistance, arterial blood pressure, and aldosterone secretion. The1H nuclear magnetic resonance spectra of human II Ang and Ang II were determined both separately and when combined in the same cuvette. The spectrum obtained by overlaying the separate spectra for these two peptides was the same as the spectrum obtained from the mixture of these two peptides in the same cuvette. These studies indicate that human, but not rat, II Ang blocks the in vivo effects of Ang II; however, this blockade is mediated by receptor antagonism and not via direct binding to Ang II.

ISSN:0194-911X    

出版商:OVID    

年代:1993

数据来源: OVID