Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neocarzinostatin (NCZ), an acidic polypeptide antibiotic, was given to 47 patients with cancer and leukemia, and tolerance to two schedules, a single dose given as a 2 hour infusion and a continuous infusion over 5 days was investigated. Immediate reactions, including fever, chills, rigor, hypertension and mental confusion, were dose-limiting for the 2 hour infusion schedule, occurring at 3000 U/m2 and higher. Continuous administration for 5 days eliminated the immediate reactions and then hematological toxicity--often prolonged leukopenia and thrombocytopenia--became dose-limiting. Other toxicities of NCZ at both dose schedules included anemia, fever and chills, anorexia, nausea and vomiting, hepatic dysfunction, azotemia, hypophosphatemia, aminoaciduria, stomatitis, phlebitis and/or cellulitis at the venous infusion site and pruritus. Patients with solid tumors who had received little or no prior chemotherapy and had good bone marrow reserve tolerated up to 6000 U/m2/24 hours X 5 days. One patient with previously treated acute myelocytic leukemia was induced into a good partial remission lasting 10 weeks.
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PMID:Phase I study with neocarzinostatin: tolerance to two hour infusion and continuous infusion. 15 43

A patient with a vipoma of the pancreas and persistently elevated blood levels of vasoactive intestinal polypeptide (VIP) had watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome). In the untreated state, the diarrhea was never profuse. Fecal volumes ranged from 0.16 to 1.24 L/day. Attempts to correct the dehydration by fluid and electrolyte loading resulted in a massive increase in fecal water and electrolyte loss. Prednisone cured the diarrhea and was associated with a decrease in plasma VIP levels. The patient had a marked circulatory disturbance with systemic arterial hypotension and cutaneous vasodilation that caused a subnormal body temperature. Removal of the tumor led to a dramatic change in the patient's circulation. Generalized vasodilation with systemic venous and arterial hypotension gave away to vasoconstriction with severe venous and arterial hypertension. Central venous pressure rose from -4.4 to +4.0 cm H2O and arterial pressure rose from 80/55 to 195/110 mm Hg. These changes might explain the unexpected and sometimes fatal heart failure that has complicated the removal of these tumors from some patients.
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PMID:Vipoma of the pancreas: observations on the diarhrhea and circulatory disturbances. 43 2

1. Renal prostaglandins act primarily as local hormones, having their effects at, or near to, sites of synthesis. PGE2 is a major determinant of renal vascular reactivity; it opposes the vasoconstrictor and natriuretic actions of pressor hormones and brakes the release of noradrenaline from adrenergic nerves. In the unanaesthetized rabbit prolonged inhibition of prostaglandin synthesis results in hypertension. In the rat, however, renal prostaglandins augment pressor stimuli. 2. Basal efflux of renal prostaglandins is positively correlated with blood flow to the inner cortex and medulla. Those stimuli which increase renal medullary blood flow do so primarily by activating prostaglandin synthetase. 3. Kinins increase prostaglandin synthesis which action modifies the renal effects of kinins. Thus, one or more renal prostaglandins contribute to the renal vasodilator action of bradykinin and mediate its effect on excretion of water as well as possibly attenuating the natriuretic action of the polypeptide. Kinins in addition to stimulating prostaglandin synthesis may determine the principal product of synthetase by regulating the enzyme PGE 9-ketoreductase, which converts PGE to PGF. The coupling of these systems within the kidney appears unique--prostaglandins mediate some of the actions of kinins and modulate others, whereas they depend on the intrarenal generation of kinins to set their level and type of activity.
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PMID:Renal prostaglandins. 82 36

Further studies are reported on the existence of a sensitizing factor in plasma of hypertensive subjects, which increases the vascular sensitivity to pressor agents when injected iv into nephrectomized rats. Plasma samples from normotensive subjects, patients with malignant hypertension, normotensive dogs, and dogs with experimental renovascular hypertension were fractionated on Bio-Gel P-10 columns after cold acetone precipitation, and on DEAE-cellulose columns eluted with sodium chloride and pH gradients. The effect of the various fractions on the vascular sensitivity to angiotensin was tested utilizing nephrectomized rats. The sensitizing activity was found only in fractions obtained from plasma of hypertensive patients and dogs and it was concentrated primarily in three fractions. Th results suggest that the sensitizing factor is negatively charged at neutral pH and it could be a polypeptide or a small protein.
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PMID:Further studies on the existence of a sensitizing factor to pressor agents in hypertension. 115 Aug 66

Several inhibitors of angiotensin converting enzyme were also found to inhibit aminopeptidase P, whereas inhibitors of other mammalian aminopeptidases were ineffective. Aminopeptidase P purified from pig kidney cortex was found to contain one atom of zinc per polypeptide chain, confirming its metalloenzyme nature. The concentrations of converting enzyme inhibitors required to cause 50% inhibition (I50) of aminopeptidase P were in the low micromolar range. The most potent converting enzyme inhibitors toward aminopeptidase P were the carboxylalkyl compounds, cilazaprilat, enalaprilat, and ramiprilat (I50 values of 3-12 microM). The sulfhydryl compounds captopril (I50 110 microM) and YS980 (I50 20 microM) were slightly less potent at inhibiting aminopeptidase P. In contrast, the carboxylalkyl compounds benazeprilat, lisinopril, and pentoprilat; the sulfhydryl compound rentiapril; and the phosphoryl compounds ceranopril and fosinoprilat had no inhibitory effect against aminopeptidase P. This compares with I50 values in the 1-6 nM range for these inhibitors with angiotensin converting enzyme. Inhibition of aminopeptidase P may account for some of the effects or side effects noted with the clinical use of converting enzyme inhibitors. These results may provide the basis for the design of more selective inhibitors of angiotensin converting enzyme or mixed inhibitors of aminopeptidase P and angiotensin converting enzyme, or both.
Hypertension 1992 Mar
PMID:Inhibition by converting enzyme inhibitors of pig kidney aminopeptidase P. 131 13

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

Effects of pituitary adenylate cyclase-activating polypeptide (PACAP38) and PACAP27 on the cardiovascular and respiratory systems were examined and compared to those of vasoactive intestinal polypeptide (VIP) in anesthetized beagle dogs. Intravenous PACAP27 and PACAP38 produced a decrease in mean arterial blood pressure (MBP), and an increase in both femoral arterial blood flow (ABF) and in frequency of respiration (FR) with a dose-dependent relationship between 10 and 300 pmol/kg. PACAP27 produced a dose-dependent increase in heart rate (HR) between 10 and 300 pmol/kg while PACAP38 induced tachycardia which was not dose-dependent. Administration of 300 pmol/kg PACAP38 and PACAP27 produced extreme hypertension after transient hypotension. PACAP38 produced severe bradycardia after transient tachycardia. The cardiovascular actions of PACAP38 were persistent compared to those of PACAP27. Intravenous injection of 10-300 pmol/kg VIP brought about hypotension, tachycardia and an increase in ABF and FR with a dose-dependent relationship. VIP, at 2000 pmol/kg, did not produce the biphasic response obtained by a large dose of PACAP38. The present studies demonstrate that PACAP partially possesses VIP-like cardiovascular and respiratory actions and that the C-terminal 11 amino acid residues of PACAP38 are presumably responsible for a prolongation of its actions.
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PMID:Cardiovascular and respiratory actions of pituitary adenylate cyclase-activating polypeptides. 143 75

Endothelin is a bioactive polypeptide released from vascular endothelium, which has a strong action promoting vascular contraction, proliferation and hypertrophy of vascular smooth muscle cells. The present investigation was performed on the hypertensive rat produced by narrowing abdominal aorta and drinking saline. It was observed that the level of plasma endothelin in the hypertensive rats was doubled (9.70 +/- 0.68 vs. sham group 4.11 +/- 0.33 pg/ml, P < 0.01), and administration of specific endothelin-antiserum into hypertensive rats significantly attenuated the increase in the blood pressure (18.97 + 1.32 vs. 27.33 + 0.09 kPa in untreated hypertensive rats, P < 0.01), and dramatically ameliorated malfunction resulting from myocardial hypertrophy. The results suggest that endothelin is an important factor in the pathogenesis of hypertension, and that inhibition of endothelin action may be a new effective way in prevention and therapy of hypertension.
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PMID:[Role of endothelin in the pathogenesis of rat experimental hypertension produced by aorta narrowing and saline uptake]. 145 61

The migration and proliferation of endothelial cells play a pivotal role in various vascular diseases. We have previously reported that atrial natriuretic polypeptide (ANP) exerts an antigrowth effect on vascular smooth muscle cells via the guanylate cyclase-coupled mechanism. Because the endothelial cells are known to possess a large number of guanylate cyclase-coupled ANP receptors, we examined the action of ANP on the growth of endothelial cells. ANP (10(-7) and 10(-6) M) significantly attenuated serum-stimulated DNA synthesis of cultured bovine aortic endothelial cells with concomitant reduction of the increase in cell number. A ring-deleted analogue of ANP exerted less prominent antiproliferative action, and 8-bromo cyclic GMP (cGMP) mimicked the action of ANP, suggesting the involvement of cGMP cascade in the endothelial growth. Moreover, the proliferative action of exogenously administered basic fibroblast growth factor on endothelial cells was significantly attenuated by the simultaneously administered 8-bromo cGMP. Taken together, the present results demonstrate a potential novel role of ANP in the regulation of endothelial cell growth, which is implicated in angiogenesis or reendothelialization.
Hypertension 1992 Jun
PMID:Atrial natriuretic polypeptide as a novel antigrowth factor of endothelial cells. 153 17

Endothelin is a newly discovered potent vasoconstrictive polypeptide released by endothelial cells in response to various stimuli, including vasoactive peptides such as angiotensin II, adrenaline and vasopressin, and thrombocyte products like transforming beta growth factor and thrombin. Endothelin is believed to exert its main effects locally, in a paracrine or autocrine way. In vascular tissue, endothelin induces longlasting contraction of smooth muscle cells, leading to decreased blood flow, especially in the coronary and renal circulation, together with an increase in systemic blood pressure. It acts also mitogenically in vascular smooth muscle cells. Endothelin stimulates release of aldosterone and catecholamines in non-vascular tissue, and inhibits release of renin. A physiological function of endothelin may be to modulate vascular tone, and increased levels of circulating endothelin are seen after the "cold pressor test". Moreover, plasma endothelin concentration is elevated during acute myocardial infarction, in acute renal failure, in patients with hypertension, and during cardiogenic chock. What role endothelin plays in the development of these conditions, and in other disorders such as vascular spasm and atherosclerosis is uncertain.
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PMID:[The endothelial cell as an endocrine organ--endothelin]. 155 33


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