摘要:

Endothelium-derived relaxing factor (EDRF) is a labile humoral agent released by vascular endotheHum that mediates the relaxation induced by some vasodilators, including acetylchollne and bradykinin. EDRF also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to vascular endotbetium. These actions of EDRF are mediated through stimulation of the soluble guanylate cydase and the consequent elevation of cyclic guanosine 3',5'-monophosphate. EDRF has been identified as nitric oxide (NO). The pharmacology of NO and EDRF is indistinguishable; furthermore, sufficient NO is released from endothellal cells to account for the biological activities of EDRF. Organic nitrates exert then- vasodilator activity following conversion to NO in vascular smooth musde cells. Thus, NO may be considered the endogenous nitrovasodilator. NO is synthesized by vascular endotheUum from the terminal guanido nitrogen atom(s) of the amino add L-arginine. This indicates the existence of an enzymic pathway in which L-arginine is the endogenous precursor for the synthesis of NO. The discovery of the release of NO by vascular endotheiial cells, the blosynthetk pathway leading to its generation, and its interaction with other vasoactive substances opens up new avenues for research into the physiology and pathophysioiogy of the vessd wall.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Increased reactivity to vasoconstrictor agents and decreased arteriolar luminal diameter have been implicated in the maintenance of hypertension. The same hamster cheek pouch microvessels were tested for angiotensin I (Ang I) and angiotensin n (Ang II) reactivity before and 10 to 14 days after Grolhnan (two-kidney, one figure-8) or sham operation. Mkrovascular geometric parameters were measured before and after a maximal vasodilator dose of adenosine. Then maximal vasoconstrictions to Ang I or Ang II were measured: Ang I and Ang II were applied adjacent to arterioles (10−2-104pmol) and venules (10−1pmol) in 10-μl abquots for 1 minute. Blood pressure (178 ± 11/133 ± 8 mm Hg) of renovascular hypertensive hamsters was elevated significantly over blood pressure of sham-operated hamsters (120 ± 11/97 ± 10 mm Hg). No change was observed in venular geometry or reactivity in renovascular hypertensive hamsters. Arteriolar luminal diameter, wall thickness, wall/lumen ratio, and wall area were not altered in hypertensive hamsters in the normal or vasodilated state; vasodilator capacity was the same in all groups. Conversion of Ang I to Ang II (response to Ang I divided by response to Ang II for first-order and third-order arterioles and third-order venules was 74 ± 5, 79 ± 3, and 72 ± 6%, respectively, and was unaltered in renovascular hypertensive hamsters. Although vessel geometry was not altered, there was a significant shift to the left of the Ang I and Ang II dose-response curves of first-order and third-order arterioles, indicating Increased sensitivity to these vasoconstrictors. Increased microvascular responsiveness to Ang n may lead to an exacerbation of renovascular hypertension during periods of increased plasma renin activity.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Vasodilator drugs are widely used in the management of cardiovascular disease. They decrease systemic vascular resistance, but they also may influence vascular arterial compliance. This study evaluated the effects of three vasodilators—nitroprusside, nltroglycerin, and hydralazine—on vascular compliance using impedance parameters determined by pulse contour and Fourier analyses. The open chest study was performed on anesthetized dogs. Mean arterial pressure decreased by a minimum of 20% after vasodilator intervention. The decrease in systemic vascular resistance was significant (p< 0.01) only after hydralazine treatment. Proximal compliance increased after administration of all drugs, but the increase was not statistically significant. Distal compliance determined by pulse contour analysis increased by 60 to 120% after all three drug treatments (p< 0.05 for nitroprusside, p < 0.02 for nitroglycerin and hydralazine). Characteristic impedance from Fourier analysis responded variably, and changes were not statistically significant. The sensitivity of changes in distal compliance as a marker for the vascular effect of these drugs suggests that it might be used as a more reliable guide than blood pressure or vascular resistance in monitoring clinical response to such intervention. The more traditional measure of characteristic impedance provides a vascular measurement that is less sensitive than distal compliance to the effects of these vasodilator drugs.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractions in response to norepinephrine. This type of oscillatory behavior does not occur in tail arteries from normotensive Wistar-Kyoto rats (WKY). We have shown that the traits of norepinephrineinduced oscillatory activity and high blood pressure are genetically associated in SHRSP, suggesting that oscillatory activity is a primary vascular abnormality that contributes to hypertension in this strain. In the present experiments, two approaches were used to test the hypothesis that adrenal mineralocorticoids modulate expression of this genetically determined vascular abnormality in SHRSP. First, the effect of adrenalectomy on blood pressure and oscillatory activity was determined in SHRSP that underwent bilateral adrenalectomy 3 weeks before experimentation. Second, the effect of deoxycorticosterone acetate (DOCA)-salt treatment on blood pressure and oscillatory activity was determined in 1) rats with no genetic background for oscillatory activity (WKY) and 2) progeny of SHRSP x WKY (F1rats). Helically cut tall artery strips from all rats were mounted in isolated tissue baths for isometric force recording. Vessels were exposed to norepinephrine (6×10−1to 6×10−6M) for 20 minutes at each concentration. Oscillatory activity was defined as the sum of the phasic contractile amplitudes for all oscillations occurring during the final 10 minutes of norepinephrine Incubation. Adrenalectomy markedly decreased blood pressure and oscillatory activity in SHRSP. DOCA-sait treatment caused hypertension in both WKY and F1rats, but oscillatory activity was observed in tall arteries only from rats with a genetic background that favors the development of oscillatory activity (F1rats). These results suggest a role for adrenal mineralocorticoids in modulation of this vascular abnormality in SHRSP.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Since both ghicocortkoids and catecholamines are involved in the regulation of normal blood pressure, we Investigated the modulation of β-adrenergic receptors of cultured rat arterial smooth muscle cells by glucocorticoids. The synthetic glucocorticoids dexamethasone and RU 28362, at 10−8M concentration, increased maximum β-adrenergic binding but had no effect on the dissociation constant (Kd). Each steroid caused an Increase in maximnm [3H]dihydroalprenolol binding over the concentration range of 10−8to 10−6M, but not at 10−2M. The glucocorticoid effect on β-adrenergk receptors of arterial smooth muscle cells required a minlmnm of 20 hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximlde (10 μg/ml), indicating that the glucocorticoid effect required protein synthesis. The effect of dexamethasone on [3H]dihydroalprenolol binding was significantly inhibited by the glucocorticoid antagonist RU 38486. Basal and agonist-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) levels In arterial smooth muscle cells, before and after glucocorticoid treatment, were measured as an indicator of the physiological significance of the observed glucocorticoidinduced increase in β-adrenergic receptor binding. While causing no change in the basal cAMP level, treatment of arterial smooth muscle cells with 10−6M dexamethasone for 24 hours increased the 10−6M isoproterenol-stimulated cAMP levels.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Free intraceUular calcium was measured in renal proximal tubules obtained from spontaneously hypertensive rats (SHR) and from age-matched Wistar-Kyoto rats (WKY) ingesting a normal diet. Experiments were performed on renal proximal tubule suspensions using fura-2 to monitor cytosolic calcium. In 4-week-old rats, when systolic blood pressure was not significantly different between the two groups, renal proximal tubule cytosolic calcium was similar (143 ± 28 and 144 ± 15 nM, respectively). By the age of 5 weeks, cytosolk calcium increased significantly in both SHR and WKY (214 ± 24 and 262 ± 34 nM, respectively, p < 0.05). Calcium, however, was not significantly different between the two groups, even though at this age blood pressure was higher in SHR than in WKY. As compared with values in 4-week-old rats, cytosolic calcium was also found increased in tubules from both SHR and WKY aged 10 to 12 weeks (261 ± 42 and 279 ± 30 nM, respectively) and 20 to 24 weeks (263 ± 42 and 308 ± 28 nM, respectively). However, no significant differences in cytosolic calcium were found between SHR and WKY even though at these ages systolic blood pressure increased markedly in the SHR. Moreover, regression analysis failed to reveal a correlation between cytosolic calcium and blood pressure when data from either group of rats of all ages studied were pooled. Exposure to ouabain (10−3M) to inhibit Na+,K+– adenosine triphosphatase and increase intracellular sodium had no significant effect on cytosolic calcium in tubules from either SHR or WKY (260 ± 69 and 250 ± 45 nM, respectively). This finding suggests that a circulating ouabainlike factor is not likely to increase cytosolic calcium in renal proximal tubules from te SHR. Our data indicate that cytosolic calcium is not elevated in renal proximal tubules obtained from the SHR either before or during sustained hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

A carboxy terminal renin complementary DNA (cDNA) clone from rat kidney was isolated, characterized, and used as a probe for renin messenger RNA (mRNA) quantification in normotensive and hypertensive rats. RNA blotting analysis detected renin mRNA in control kidney and brain. Deoxycorticosterone acetate (DOCA) and high salt (1 %) treatment of experimental gnimnls resulted in a greater than 95% decrease in the content of renin mRNA in the kidney, as compared with values in control rats receiving 0.4% NaCl in their diet. In contrast, high salt (1%) treatment alone caused only a twofold decrease in kidney renin mRNA content, as compared with values in controls. DOCA and low salt (0.04%) or low salt (0.04%) treatment alone caused a 1.5-fold Increase in the kidney renin mRNA content, as compared with values in control rats. These results indicate that DOCA and salt have a synergistic effect in depressing renin mRNA levels in kidney. Clipping of the left renal artery caused a threefold increase in the steady state level of renin mRNA in the iscbemic kidney and a 0.5-fold decrease in the hypertrophied kidney. The data are consistent with the hypothesis that blood pressure and other stimuli regulate the expression of the renin gene in vivo.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

In renovascular hypertension adaptive mechanisms in the poststenotk kidney are a probable cause of the 20 to 25% false-negative findings during rapid sequence urography or [123I]oiodohippurate renography. We blocked the renin-angiotensin system in an effort to increase the yield of these diagnostic procedures. Chronically instrumented, salt-depleted conscious dogs were used in which a light (n= 5), moderate (n= 4), or severe (n= 2) renal artery stenosis was induced. Before stenosis 10 of the dogs showed no left-right differences with either diagnostic procedure, and angiotensin converting enzyme (ACE) inhibition did not change this result. Two to 3 weeks after induction of a renal artery stenosis, all dogs showed signs of renovascular hypertension. However, only 50% of the renograms and 22% of the urograms showed differences between the two kidneys indicative of the presence of stenosis. After ACE inhibition, all previously negative test results became positive (abnormal) and previously existing left-right differences became more evident. Ekctromagnetically measured renal blood Bow on the stenotic side did not change during ACE inhibition (146 ± 13 vs 145 ± 21 ml/mm), whereas contralateral blood flow showed a distinct increase (207 ± 18 vs 282 ± 20 ml/min, p < 0.01). In conclusion, ACE Inhibition markedly improves the sensitivity of rapid sequence urography and hlppurate renography in the diagnosis of renovascular hypertension in the two-kidney, one clip Goldblatt hypertensive dog. The effects of ACE inhibition on the handling of the different tracers do not appear to be related to its effects on renal blood flow or systemic blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

This study examined the contribution of the endothelium to pressor and depressor responses in the isolated, perfused mesentery of mineralocorticoid hypertensive rats. Following uninephrectomy, adult male rats were made hypertensive by subcutaneous implantation of deoxycorticosterone acetate (DOCA; 200 mg/kg); control rats were sham-treated. All rats received drinking water that contained 1.0% NaCl and 0.2% KC1. Following 4 to 6 weeks of treatment, the rats were anesthetized and the mesenteric vasculature was isolated and pump-perfused (constant flow with buffer) to evaluate changes in perfuskm pressure. Vascular responses were determined before and after disruption of endothelial function by perfuslon with oxygen free radicals generated in the buffer by electrical stimulation. Vasodilator responsiveness to acetylcholine and nitroprusside in the intact mesentery of hypertensive rats did not differ from that in the intact mesentery of nonnotensive rats, whereas pressor responses to norepinephrine in the intact mesentery of hypertensive rats were greater than nonnotensive values. Fllowing disruption of endothelial function, depressor responses to acetylcholine were greatly attenuated whereas those to nitroprusside were unaltered or increased. Pressor responses to norepinephrine were potentiated in mesentery that had undergone endothelial disruption, and this potentiation was greater in hypertensive rats than in control rats. The slopes of pressure-flow curves in the presence of norepinephrine were less steep in mesentery with intact endothelium. The flow-modified component of these pressure-flow curves that was related to the endothelium was greater in mesenteric vascular beds of hypertensive rats. These results Indicate that a factor released from the endothelium partially masks the enhanced vascular reactivity characteristic of this animal model of mineralocortkoid hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Specific atrial natriuretic factor (ANF) analogues have been found to have inhibitory activity in vitro in a calmodolin-dependent, human red blood cell membrane Ca2+-adeoosine triphosphatase (ATPase) model. Studied at 10−3to 10−6M concentrations, atriopeptin I (residues 127–147 of rat prepro-ANF sequence) and atriopeptin in (residues 127–150) progressively inhibited Ca2+-ATPase activity by up to 20% (p< 0.001). This degree of inhibition was consistent with activities of other (calmodulin-independent) enzyme inhibitors in this model. Therefore, the C-tenninal Phe-Arg-Tyr sequence (residues 148–150) Is unnecessary for atriopeptin action on Ca2+-ATPase. Human and rat atrial peptides with amino acids 123–150 were inactive, indicating that the 123–126 sequence (Ser-Leu-Arg-Arg) must be cleaved to activate atriopeptins in this system. Human ANF fragment 129–150 also had no effect on Ca2+-ATPase, defining the importance of residues 127–128 (Ser-Ser) proximal to the disulfide bridge (Joining 129 to 145). The addition of purified calmodulin to red blood cell membranes in the presence of inhibitory ANF did not restore Ca2+-ATPase activity to normal levels, Indicating that the ANF effect on this enzyme is calmodulin-independent. Atriopeptin I and atriopeptin IN had no effect on red blood cell Na+,K+-ATPase activity in vitro. Thus, the structure-activity relationships of ANF analogues in this novel human cell membrane model are highly specific. Although the inhibitory action of ANF analogues on Ca2+-ATPase, a calcium pump-associated enzyme, may be unique to the red blood cell, the calcium dependence of the gluconeogenic effects of ANF in the kidney would be supported by inhibition of this ATPase.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID