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

Alterations in neurohormonal response are a widely-observed feature in various forms of hypertension. Such responses depend not only on levels of hormones/neurotransmitters, but also on receptors and post-receptor components. With respect to G protein-coupled receptors, such as those for catecholamines, angiotensin II, and bradykinin, it is possible that G-proteins or G protein-coupled effector molecules are altered in hypertension. In this article, several classes of G alpha proteins and effectors which link to these proteins are briefly discussed. Evidence is presented in support of the concept that signal amplification in G protein-coupled receptor systems occurs at the level of receptor activation of the G proteins. Limited data are as yet available that directly assess whether changes in the amount or properties of particular G alpha proteins or G-protein-linked effectors, are altered in hypertension. The availability of antibody, cDNA and other genetic probes should prove highly useful in testing the hypothesis that such alterations are important for the pathogenesis and maintenance of the hypertensive state.
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PMID:GTP-binding proteins and post-receptor components in hypertension. 138 Jul 10

Inhibitors of the angiotensin converting enzyme (ACE, EC 3.4.15.1) are important in the treatment of the high blood pressure. The therapeutically used drugs captopril, enalapril and ramipril are enzymatic stable short pseudo-peptides. They are stabilized against enzymatic degradation and therefore usefully for oral application. But for some indications e.g. post operative treatment and shock therapy well dosed infusions are needed. For this purpose we attached nona-, penta- and tripeptide inhibitors of the ACE to immunologically inert dextran polymers. The inhibitors are derived as well from the bradykinin potentiating nonapeptide BPP9 alpha (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) and the bradykinin potentiating pentapeptide BPP5 alpha (Pyr-Lys-Trp-Ala-Pro), both originally isolated from snake venoms, as from acylated tripeptides with the structure Acyl-AA1-Arg-Pro. We estimated the influence on the biological activity of two different linkers to the dextran polymers. The coupling to the polymer was achieved on the one hand via the aldehyd moiety (DAD-AK) and on the other hand by the carboxyl residue (KMD). In the case of DAD-AK-polymers the condensation of the peptides was performed by the N-hydroxysuccinimide ester of the polymer. Because of the instability of the KMD-OSU in this case water soluble carbodiimides are used. The polymer bound peptides inhibit the isolated ACE, but in the most cases with a reduced activity. Only the tripeptide DPhe-Arg-Pro has a enhanced activity in the polymer bound state. The polymer bound inhibitors show a prolongated action on normotensive rats by intravenous application.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Peptide inhibitors of the renin-angiotensin system. 2. Polymer-bound tri-, penta- and nonapeptide inhibitors of angiotensin converting enzyme]. 138 10

It has been reported that atrial natriuretic peptide (ANP) concentrations are elevated in pregnancy and further elevated in pregnancy-induced hypertension. Atrial stretch and volume expansion appear to be important stimuli for ANP release. During normal pregnancy, a striking change in hemodynamics occurs that may increase plasma ANP concentrations. ANP has potent natriuretic, diuretic, and smooth muscle relaxant activities. The biological effects of ANP during pregnancy may play an important role in the physiology and pathophysiology of pregnancy. Because of possible interactions during pregnancy due to secondary effects of maternal cardiovascular changes and physiological adaptation, the present study sought to evaluate and characterize the local effects of atriopeptin II on the uterine vascular bed of the nonpregnant sheep. Ewes with catheters in the femoral artery, femoral vein, and uterine artery and electromagnetic flow probes on the middle uterine arteries were monitored for blood pressure (BP), heart rate (HR), and uterine blood flow before and after the administration into the uterine artery of bolus injections of 2, 4, 20, and 40 x 10(-9) M (5, 10, 50, and 100 micrograms) of the synthetic ANP (atriopeptin II). For comparison purposes, the effects of prostaglandin I2 in doses of 1.2, 2.5, 12, and 25 x 10(-8) M (5, 10, 50, and 100 micrograms), vasoactive intestinal polypeptide in doses of 3, 9, 30, 90, 300, and 900 x 10(-11) M (0.1, 0.3, 1, 3, 10, and 30 micrograms), and bradykinin in doses of 9.4, 28, 94, 280, 940, and 2800 x 10(-11) M (0.1, 0.3, 1, 3, 10, and 30 micrograms) were also tested. Appropriate vehicles were tested and found to be without effect. All four compounds were found to be vasodilators of the nonpregnant uterine vasculature. ANP administered into the uterine artery decreased BP (87 +/- 4 mm Hg to 79 +/- 4 mm Hg with 50 micrograms [20 x 10(-9) M]), increased HR (90 +/- 5 bpm to 105 +/- 4 bpm), and significantly increased uterine blood flow (from 14 +/- 3 to 37 +/- 4 ml/min with a dose of 100 micrograms [40 x 10(-8) M, P < 0.05]). Prostaglandin I2 failed to alter BP, but caused significant increases on HR (100 +/- 4 to 124 +/- 13 bpm, P < 0.05) and uterine blood flow (17 +/- 4 to 73 +/- 10 ml/min, P < 0.05). Vasoactive intestinal polypeptide caused a significant tachycardia (97 +/- 10 to 158 +/- 9 bpm, P < 0.05) at the highest dose.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of atrial natriuretic peptide and other vasoactive compounds on the uterine vascular bed of the nonpregnant sheep. 143 42

A double-blind, randomized, cross-over, placebo-controlled study was carried out to determine the extent and duration of potentiation of the action of bradykinin introduced intradermally by a long-acting novel angiotensin converting enzyme (ACE) inhibitor, trandolapril. The investigations were performed in a temperature and humidity-controlled laboratory. Intradermal injections of 1 microgram, 2.5 micrograms and 5 micrograms of bradykinin and normal saline (as control) were made into the forearm skin of eight healthy normotensive male volunteers aged 21-33 years (mean 28 years) at baseline, 2, 4, 8, 24, 48, 72 and 96 hours after either 2 mg trandolapril or placebo given orally. Skin blood flow outside the induced weal was monitored by laser Doppler flowmetry (mean of recordings at four sites adjacent to the weal within the flare area). Flare area and weal volume were also measured. Trandolapril reduced the mean arterial pressure. However, there was no evidence that this activity was associated with a potentiation of the cutaneous action of bradykinin. In conclusion, it would appear that potentiation of the action of bradykinin may not be an important contributing factor to the fall in total peripheral vascular resistance associated with ACE inhibition in humans in the control of hypertension.
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PMID:Absence of potentiation of the skin response to intradermal bradykinin by a long-acting angiotensin converting enzyme inhibitor, trandolapril, at conventional antihypertensive dosage in human volunteers: a double-blind, randomized, cross-over, placebo-controlled trial. 148 May 37

The goal of the present study was to compare the hemodynamic and biochemical effects of the renin inhibitor Ro 42-5892, the angiotensin converting enzyme inhibitor cilazapril, and the angiotensin II receptor blocker EXP132, the aldehyde derivative of DuP 753. The three drugs were evaluated in guinea pigs, previously treated with furosemide, using their maximal effective doses. Cilazapril decreased arterial blood pressure more than Ro 42-5892 and EXP132. In contrast, Ro 42-5892 and EXP132 had similar effects. The larger decrease of arterial pressure induced by cilazapril was not due to a larger decrease of angiotensin II in plasma and was not influenced by cyclooxygenase inhibition with indomethacin or by bradykinin antagonism with Hoe 140. After binephrectomy, most of the blood pressure-lowering effect of Ro 42-5892 disappeared. In contrast, cilazapril was still markedly effective, pointing to extrarenal effects. We conclude that in furosemide-treated guinea pigs, as opposed to previously published animal models, the decrease of arterial pressure induced by angiotensin converting enzyme inhibitors may be partly due to extrarenal effects not related to the renin-angiotensin system.
Hypertension 1992 Mar
PMID:Effects of renin-angiotensin system blockade in guinea pigs. 153 64

We have previously demonstrated that loss of renal functional reserve (renal response to protein loading) in two-kidney, one clip Goldblatt hypertension is characterized by no change in glomerular filtration rate or single nephron glomerular filtration rate and decreased absolute proximal tubular reabsorption during glycine administration. Captopril restores proximal reabsorption and renal functional reserve in this condition. Because captopril suppresses angiotensin II generation and increases bradykinin, prostaglandins, and potentially nitric oxide, we have investigated the role of angiotensin II blockade in restoring proximal reabsorption and renal functional reserve by comparing captopril with DuP 753, an angiotensin II receptor antagonist, in Goldblatt rats. One month after clipping, two period micropuncture studies (control and glycine) were performed on the unclipped kidney. Normal rats and three groups of clipped rats were studied: an untreated group (HYP), a group treated with captopril (CEI), and a group treated with DuP 753 (DuP) 5 days before micropuncture. Glycine increased glomerular filtration rate, nephron plasma flow, and single nephron glomerular filtration rate in normal rats. Systemic and glomerular hypertension in HYP rats was associated with loss of renal functional reserve and a decrease in absolute proximal reabsorption during glycine. Captopril and DuP 753 normalized systemic and glomerular capillary pressure and prevented the decrease in proximal reabsorption during glycine; however, only CEI rats increased single nephron glomerular filtration rate and glomerular filtration rate after glycine. In conclusion, abnormal responses of both glomerular and tubular function are responsible for the loss of renal functional reserve in Goldblatt rats. Inhibitory angiotensin II activity is responsible for decreasing proximal reabsorption during glycine; however, factors other than angiotensin II limit the glomerular response to glycine.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Jun
PMID:Angiotensin II and renal functional reserve in rats with Goldblatt hypertension. 159 82

Electrical stimulation of afferent renal nerves and activation of renal mechanoreceptors increase plasma vasopressin concentrations. In the present study, the effect of renal chemoreceptor activation on plasma vasopressin concentration was investigated in anesthetized rabbits. Renal chemoreceptors were activated with intrarenal infusions of bradykinin. With intrarenal infusion of bradykinin at 136 ng/min, plasma vasopressin concentration increased from 4.5 +/- 1.5 to 26.8 +/- 14.2 pg/ml at 5 minutes (p less than 0.01), whereas with infusion at 1,360 ng/min, plasma vasopressin increased from 5.9 +/- 2.0 to 54.4 +/- 16.4 pg/ml at 5 minutes (p less than 0.01). There was no significant change in plasma vasopressin during intravenous infusion of bradykinin at 136 ng/min. Infusion at 1,360 ng/min increased plasma vasopressin from 2.7 +/- 0.5 to 14.8 +/- 6.4 pg/ml (p less than 0.01), but this increase was significantly less than that produced by intrarenal infusion of the same dose of bradykinin. Similar effects on plasma vasopressin were observed during paired intrarenal and intravenous infusions of bradykinin at 136 ng/min. Renal denervation markedly reduced the vasopressin responses to intrarenal infusion of bradykinin at 136 ng/min (2.8 +/- 0.5 to 4.0 +/- 0.7 pg/ml, p less than 0.01) and 1,360 ng/min (3.2 +/- 0.7 to 7.8 +/- 1.8 pg/ml, p less than 0.05). These results indicate that bradykinin stimulates vasopressin release by an intrarenal action and suggest that this action is mediated by afferent renal nerves.
Hypertension 1992 Jun
PMID:Effect of intrarenal bradykinin infusion on vasopressin release in rabbits. 159 84

Vasodilatory responses to bradykinin (BK) and acetylcholine (ACh) were compared in phenylephrine preconstricted perfused kidneys from 30-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Responses to ACh did not differ between kidneys from SHRSP and WHY. BK-induced dilatation was greater in kidneys from SHRSP relative to WHY and was not affected by indomethacin or captopril. These results indicate that renal vasodilatory responsiveness to bradykinin is enhanced in SHRSP with established hypertension.
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PMID:Enhanced vasodilatory responses to bradykinin in stroke-prone spontaneously hypertensive rats. 160 Oct 60

Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR.
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PMID:Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat. 160 8

The vascular endothelial cells have the ability to modulate local vascular tone by releasing relaxing factors such as nitric oxide or the vasoconstrictor peptide endothelin-1. Although this regulatory system is found in all vertebrates, there is a great heterogeneity in the release of these endothelium-derived substances, from one organ to an other, between large and small vessels, and between different species. Therefore, observations made in certain vascular beds or animals do not necessarily apply to human ophthalmic circulation. The present study was designed to investigate endothelial mediators in the human ophthalmic artery. The results show that in the human ophthalmic artery, nitric oxide is released under basal conditions and that its production can be markedly stimulated by bradykinin, acetylcholine, and particularly histamine, which cause profound vascular relaxation. In contrast, endothelin-1 evoked potent contractions, which were unaffected by the calcium antagonist nifedipine. However, upon re-exposure of the blood vessels to the peptide, marked tachyphylaxis occurred. These findings demonstrate that in the human ophthalmic artery, endothelium-derived nitric oxide and endothelin are very potent modulators of vascular tone, suggesting that they play an important role in the regulation of local blood flow in the eye. Hence, endothelium dysfunction may represent a new pathogenetic mechanism in disease states associated with altered blood flow to the eye, such as diabetes, hypertension, and some forms of low-tension glaucoma.
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PMID:Nitric oxide and endothelin-1 are important regulators of human ophthalmic artery. 160 46


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