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

Saralasin is a highly soluble and stable AII antagonist with a relatively short half-life; therefore, its effects are rapidly reversible when administered i.v. Acute and subacute studies have shown only transient toxicosis with no significant pathology or teratology. Saralasin's angiotensin receptor affinity has been correlated with its biologic acitivity. Observations from the pharmacodynamic investigations have shown that saralasin is a specific competitive antagonist of the vascular, renal, adrenal, cardiac, and central nervous system actions of AII. In addition, these studies further support the utility of saralasin as a diagnostic and therapeutic agent for patients whose hypertension is due directly to AII.
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PMID:Preclinical pharmacology of saralasin. 11 8

Endothelium-derived relaxing factor has been shown to regulate renal blood flow, and inhibition of its synthesis increases blood pressure and renal vascular resistance and decreases renal blood flow. Using the substrate antagonist NW-nitro-L-arginine methyl ester (L-NAME), we tested whether renal vasoconstriction induced by endothelium-derived relaxing factor synthesis inhibition could be mediated in part by angiotensin II. In 14 control rats, 10 mg/kg body wt L-NAME increased blood pressure from 106 +/- 6 to 126 +/- 6 mm Hg (p < 0.001), increased renal vascular resistance by 74% (from 19.3 +/- 2.6 to 33.6 +/- 2.9 resistance units), and decreased renal blood flow by 34% (from 5.9 +/- 0.5 to 3.9 +/- 0.3 ml.min-1.g kidney wt-1, p < 0.005). When six rats were treated with 10 mg/kg body wt of the angiotensin receptor antagonist DuP 753, L-NAME increased blood pressure from 84 +/- 4 to 106 +/- 4 mm Hg (p < 0.001); however, renal vascular resistance increased by only 27% (from 13 +/- 2 to 17 +/- 3 resistance units, p < 0.01; p < 0.05 different from control value) and renal blood flow was unchanged. Likewise, after pretreatment of six rats with 32 micrograms/100 g body wt of the angiotensin converting enzyme inhibitor enalaprilat, L-NAME increased blood pressure from 88 +/- 5 to 124 +/- 6 mm Hg (p < 0.001) and renal vascular resistance by 54% (from 12 +/- 1 to 18 +/- 3 resistance units, p < 0.01; p < 0.05 different from control value) but renal blood flow was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Nov
PMID:Angiotensin dependence of endothelium-mediated renal hemodynamics. 133 Sep 22

The central cardiovascular and dipsogenic effects of angiotensin II involve interactions with norepinephrine, dopamine, and serotonin. Our findings that angiotensin II receptors and substance P immunoreactivity show a parallel distribution in the dorsal medulla and that angiotensin II releases substance P from perfused rat medulla slices revealed the potential for a functional relation between these peptidergic systems as well. Additional evidence suggests that the heptapeptide angiotensin-(1-7) exerts its biological activities via selective angiotensin receptor subtypes. Thus, we compared the effects of these two peptides on release of substance P and monoamines in perfused slices of medulla and hypothalamus from 77 male Sprague-Dawley rats. Transmitter levels were determined in 6-minute collections of perfusate before (basal), during (experimental), and after (recovery) perfusion with either angiotensin-(1-7), angiotensin II, or Krebs' solution alone (control). Substance P was measured by radioimmunoassay and monoamines and their metabolites by high-performance liquid chromatography with electrochemical detection. In the medulla, 2 microM angiotensin II but not angiotensin-(1-7) significantly increased efflux of substance P (221 +/- 87% of basal) and norepinephrine (130 +/- 17% of basal) during the experimental period. The effect of angiotensin II on substance P was sustained into the recovery period. Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were not detected in this brain region. In the hypothalamus, both angiotensin-(1-7) and angiotensin II increased substance P (169 +/- 30% and 141 +/- 35% of basal, respectively); the effect of angiotensin II was sustained throughout the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Differential actions of angiotensin II and angiotensin-(1-7) on transmitter release. 134 28

Considerable evidence now indicates that a separate and distinct renin-angiotensin system (RAS) is present within the brain. The necessary precursors and enzymes required for the formation and degradation of the biologically active forms of angiotensins have been identified in brain tissues as have angiotensin binding sites. Although this brain RAS appears to be regulated independently from the peripheral RAS, circulating angiotensins do exert a portion of their actions via stimulation of brain angiotensin receptors located in circumventricular organs. These circumventricular organs are located in the proximity of brain ventricles, are richly vascularized and possess a reduced blood-brain barrier thus permitting accessibility by peptides. In this way the brain RAS interacts with other neurotransmitter and neuromodulator systems and contributes to the regulation of blood pressure, body fluid homeostasis, cyclicity of reproductive hormones and sexual behavior, and perhaps plays a role in other functions such as memory acquisition and recall, sensory acuity including pain perception and exploratory behavior. An overactive brain RAS has been identified as one of the factors contributing to the pathogenesis and maintenance of hypertension in the spontaneously hypertensive rat (SHR) model of human essential hypertension. Oral treatment with angiotensin-converting enzyme inhibitors, which interfere with the formation of angiotensin II, prevents the development of hypertension in young SHR by acting, at least in part, upon the brain RAS. Delivery of converting enzyme inhibitors or specific angiotensin receptor antagonists into the brain significantly reduces blood pressure in adult SHR. Thus, if the SHR is an appropriate model of human essential hypertension (there is controversy concerning its usefulness), the potential contribution of the brain RAS to this dysfunction must be considered during the development of future antihypertensive compounds.
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PMID:Regulatory role of brain angiotensins in the control of physiological and behavioral responses. 136 94

The role of angiotensin receptor subtypes 1 and 2 was assessed on neointima formation after injury in rat carotid artery. The effects of angiotensin converting enzyme inhibition by perindopril (3 mg.kg-1 x day-1 p.o.) and selective blockade of angiotensin subtype 1 receptors by DuP 753 (5 and 30 mg.kg-1 x day-1 p.o.) were compared on proliferative response to balloon injury. In rats treated 6 days before and for 14 days after injury, perindopril significantly reduced (-76%, p < 0.01) myointimal hyperplasia. In contrast, DuP 753 at 5 mg.kg-1 x day-1 did not modify the hyperplastic response to balloon catheterization. Only at 30 mg.kg-1 x day-1 was DuP 753 able to reduce neointima formation (-47%, p < 0.05). This dose was equipotent to perindopril on the renin-angiotensin system as assessed by the pressor response to angiotensin II and angiotensin I. Therefore, blockade of subtype 1 receptors was a less effective means of suppression of myointimal growth than angiotensin converting enzyme inhibition, suggesting that another angiotensin receptor subtype or converting enzyme substrates are involved in this process. For the determination of whether angiotensin subtype 2 receptors were implicated, the specific subtype 2 receptor antagonist CGP 42112A (1 mg.kg-1 x day-1) was continuously infused perivascularly for 14 days in the vicinity of the injured carotid artery. CGP 42112A was as effective in preventing neointima formation as perindopril (-73%, p < 0.01, versus -76%, p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Dec
PMID:Role of angiotensin subtype 2 receptor in neointima formation after vascular injury. 145 89

2-n-Butyl-4-chloro-5-hydroxy-methyl-1-[(2'-(1H)-tetrazol-5-yl)biph enyl-4- yl)methyl]imidazol potassium salt (DuP 753) is a nonpeptide angiotensin II receptor antagonist that inhibits the contractile effects of angiotensin II competitively and shows pA2 values of 8.27 on the rabbit aorta and jugular vein, 8.66 on the rat portal vein and stomach, 8.19 on the rat urinary bladder, and 8.36 on human colon, ileum, and urinary bladder. This agent (more than 10(-5) M) exhibits no agonistic activity and does not affect the contractile effects of norepinephrine, acetylcholine, bradykinin, desArg9-bradykinin, substance P, neurokinin A, neurokinin B, or bombesin in the various tissues. The present results demonstrate that DuP 753 is a potent nonpeptide antagonist with high affinity, specificity, and selectivity for the angiotensin receptor.
Hypertension 1991 Apr
PMID:DuP 753 is a specific antagonist for the angiotensin receptor. 167 62

Adenosine is an inhibitory neuromodulator in several brain regions. In the nucleus tractus solitarius (NTS), however, adenosine exerts excitatory cardiovascular effects. The purpose of the present study was to elucidate the involvement of other endogenous mechanisms that could contribute to the final hemodynamic response to adenosine in this nucleus. In normotensive Sprague-Dawley rats, intra-NTS microinjection of adenosine (2.3 nmol/60 nl) decreased blood pressure and heart rate. These effects were blocked by prior administration of the specific adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (0.92 nmol) and by the two glutamate receptor antagonists kynurenic acid and glutamic diethylester. The specificity of the adenosine-glutamate interaction in the NTS was demonstrated with adrenergic and angiotensin receptor antagonists that did not affect the adenosine response and by experiments with glutamate receptor antagonists that did not affect nicotine actions in the NTS. Furthermore, an increase in glutamate levels was demonstrated during perfusion of adenosine through a microdialysis probe in the NTS of anesthetized rabbits. These findings indicate that adenosine increases the release of glutamate in the NTS and, thus, are at variance with the concept of a "universal" inhibitory effect of adenosine in the central nervous system.
Hypertension 1991 Oct
PMID:Cardiovascular excitatory effects of adenosine in the nucleus of the solitary tract. 168 Aug 12

Angiotensin II stimulates prostaglandin release in blood vessels via activation of angiotensin receptors present in endothelium, vascular smooth muscle cells, or both. We evaluated the response of angiotensin II, angiotensin I, and [des-Phe8] angiotensin II [angiotensin-(1-7)] on prostaglandin release in porcine aortic endothelial cells. Incubation of cell monolayers with angiotensin I and angiotensin-(1-7), but not angiotensin II, stimulated the release of prostaglandin E2 and prostaglandin I2 in a dose-dependent manner (10(-10) to 10(-6) M) with an EC50 of approximately 1 nM. In addition, we characterized the angiotensin receptor subtypes mediating prostaglandin synthesis by using subtype-selective antagonists. Angiotensin I-stimulated prostaglandin synthesis was not altered by either of the nonselective classical angiotensin receptor antagonists [Sar1,Thr8]angiotensin II or [Sar1,Ile8]angiotensin II. In contrast, either the angiotensin subtype 1 (AT1) antagonist DuP 753 or the subtype 2 (AT2) antagonist CGP42112A significantly attenuated the prostaglandin release in response to angiotensin I. However, PD123177, another AT2 antagonist, did not inhibit angiotensin I-stimulated prostaglandin release. Angiotensin-(1-7)-induced prostaglandin release was significantly attenuated by [Sar1,Thr8]angiotensin II (10(-6) M) and PD123177 (10(-6) M) but not by [Sar1,Ile8]angiotensin II, DuP 753, or CGP42112A. Higher doses (10(-5) M) of DuP 753 and CGP42112A attenuated the angiotensin-(1-7) response. These data suggest that in porcine aortic endothelial cells, angiotensin I and angiotensin-(1-7) but not angiotensin II are potent stimuli for prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors. 173 95

The ability of angiotensin peptides to stimulate prostaglandin release and raise intracellular calcium levels by activating a phosphoinositide-specific phospholipase C was assessed in three human astrocytoma cell lines (CRTG3, STTG1, and WITG2). The addition of angiotensin II to CRTG3 cells resulted in a dose-dependent release of prostaglandin E2 and prostacyclin, the production of inositol 1,4,5-trisphosphate, and the mobilization of intracellular calcium. Angiotensin-(1-7), previously considered to be an inactive metabolite of angiotensin II, was as potent as angiotensin II for prostaglandin release but did not activate phospholipase C or mobilize intracellular calcium. In contrast, angiotensin-(2-8) caused only a slight increase in prostaglandin release, even though it was as effective as angiotensin II in augmenting inositol 1,4,5-trisphosphate production and calcium mobilization. Moreover, neither the release of prostaglandins in response to angiotensin II or angiotensin-(1-7) nor the mobilization of intracellular calcium in response to angiotensin II required extracellular calcium. Angiotensin II and angiotensin-(1-7) caused the release of prostaglandins from all three human astrocytoma cell lines, but changes in the level of intracellular calcium in response to angiotensin II only occurred in CRTG3 cells. Although previous studies have provided evidence for angiotensin receptor subtypes on the basis of selectivity of antagonists or signal transduction mechanisms, these data suggest that human astrocytes contain multiple angiotensin receptor subtypes on the basis of their response to different angiotensin heptapeptides--angiotensin-(1-7) and angiotensin-(2-8).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Jul
PMID:Human astrocytes contain two distinct angiotensin receptor subtypes. 186 Jul 9

The aim of this study was to investigate the action of the heptapeptide angiotensin-(1-7) on the spontaneous activity of paraventricular neurons using microiontophoresis. Recent immunocytochemical investigations have shown that this product of angiotensin I is predominantly located in cells and fibers of the forebrain and brain stem. Our results show that most neurons in the paraventricular nucleus are excited by angiotensin-(1-7) at a dose of 50-80 nA. In comparison with angiotensin II or angiotensin III, the onset of response and the occurrence of the maximal effect were significantly delayed. With higher doses of angiotensin-(1-7), there was a decrease in latency and a dose-dependent increase in firing frequency. Of all the angiotensin compounds tested, angiotensin III was the most potent. Preliminary results obtained with an angiotensin antagonist show that the action of angiotensin II, angiotensin III, and angiotensin-(1-7) is blocked by the angiotensin receptor subtype 2 antagonist CGP 42112A. Because the angiotensin-(1-7) system in the brain is associated with central vasopressinergic pathways, vasopressin was tested in a similar way. Neurons in the paraventricular nucleus that were excited by iontophoretically applied angiotensins showed a weak response to vasopressin. Occasionally, a small excitatory action was observed. Our results support the hypothesis that the heptapeptide angiotensin-(1-7) is a biologically active neuropeptide. The data also suggest that amino terminal fragments of angiotensin II are not inactive degradation products.
Hypertension 1991 Jun
PMID:Neurophysiological responses to angiotensin-(1-7). 204 57


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