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)

The prostaglandins are potent vasoactive fatty acids that are ubiquitously distributed throughout the body. It is now well established that the prostaglandins participate in a variety of pathophysiological processes such as inflammation, burns, renal aspects of hypertension, peptic ulcer disease, diarrhea, skin conditions, vasomotor dysfunctions, platelet abnormalities, dysmenorrhea, fever, and shock. We have previously shown that the prostaglandins appeared to be elevated and were related to the circulatory dysfunction in canine and baboon endotoxin shock. In addition, our studies demonstrated that indomethacin, a prostaglandin synthetase inhibitor, not only inhibited the prostaglandin release and improved the hemodynamic derangements, but also significantly improved the survival. Indomethacin clearly improved the survival in baboon endotoxin shock even when administered after shock had occurred. Since the previous studies were in endotoxin models, the next logical step was to determine the effects of indomethacin in a clinically-relevant rat sepsis model. Two hundred sixty-six male rats (250-500 g) were randomly allocated to saline treated controls or to indomethacin treatment. A pure suspension of live E. Coli organisms (225 X 10(10)/rat) were injected i.p. to each rat. Treatment was introduced at three hours when all blood cultures were positive. Groups were divided into gentamicin (4 mg/kg/rat) alone, gentamicin and indomethacin (3 mg/kg), or indomethacin alone in addition to the saline treated controls. Results showed that indomethacin in combination with gentamicin significantly (p = 0.05) improved the survival at 24 (90%) and 48 hours (90%), when compared with saline treated controls (65%, 45%) and with gentamicin (40%, 40%). Indomethacin alone significantly (p = 0.01) improved the survival. Conclusions are that (i) therapeutic doses of indomethacin or gentamycin clearly improved the survival in a clinically relevant rat sepsis model; (ii) the exact mechanism of protection with indomethacin is unknown; and (iii) indomethacin should be considered for use in human clinical sepsis.
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PMID:The role of prostaglandins in sepsis. 704 14

Cytoplasmic microtubules appear to play a role in the secretion of a variety of protein and protein hormones. Involvement of microtubules in renin secretion has been hypothesized but not established. The present studies were designed to determine: 1) if the antimicrotubule drug, colchicine, would alter plasma renin concentration (PRC); and 2) if changes in PRC could be related to an effect on cytoplasmic microtubules. Dose response experiments in Sprague-Dawley rats showed that 0.4 or 0.8 mg/kg/day i.p. of colchicine for 3 days significantly increased PRC while a dose of 0.2 mg/kg/day was without effect. The increase in PRC at the higher doses was associated with toxicity of the drug. In other experiments, rats pretreated with colchicine (0.2 mg/kg/day) or saline received either furosemide (5 mg/kg) or isoproterenol (25 micrograms/rat) i.p. to stimulate renin secretion. Colchicine at a dose that did not alter basal PRC significantly inhibited an increase in PRC after stimulation with either isoproterenol or furosemide. Lumicolchicine, a structural isomer of colchicine without antimicrotubule activity, did not alter the response to isoproterenol stimulation. These data suggest that microtubules play a role in the increase in renin secretion following stimulation.
Hypertension
PMID:Effect of colchicine on drug-induced changes in plasma renin concentration in rats. 704 20

This study describes the effect of heparin on blood pressure, cardiac output, and total peripheral resistance in spontaneously hypertensive and one-kidney, one clip Goldblatt hypertensive rats. Administration of heparin (200 units/day/rat) for 8 weeks to young (6-week-old) spontaneously hypertensive rats (SHR) resulted in an attenuated rise in blood pressure; mean blood pressure in heparin-treated SHR (180 +/- mm Hg) was significantly lower (p less than 0.05) than that in control SHR (205 +/- 7 mm Hg). Similar heparin treatment started immediately after the induction of one-kidney, one clip (Goldblatt) hypertension reduced the rise in blood pressure. After 4 weeks of treatment, heparin-treated Goldblatt hypertensive rats had much lower blood pressure (150 +/- 4 mm Hg) than did control rats (7178 +/- 8 mm Hg). The difference was highly significant (p less than 0.01). Similarly, heparin treatment also lowered the blood pressure in rats with developed Goldblatt hypertension. After the cessation of heparin treatment, the blood pressure returned to pretreatment level in these rats. When compared to vehicle-treated rats, heparin-treated animals with either spontaneous or Goldblatt hypertension concomitantly exhibited a significant increase in cardiac output, and significant decreases in total peripheral resistance and packed cell volume. Further, the left ventricular weight to body weight ratio was significantly lower (p less than 0.05) in heparin-treated than control animals. Since a relationship seems to exist between an increase in packed cell volume and blood viscosity and the rise in arterial pressure, this blood-pressure-lowering effect of heparin may be attributed to a decrease in packed cell volume.
Hypertension
PMID:Heparin lowers the blood pressure in hypertensive rats. 710 35

A number of injurious agents, including "load-failure" of hemodynamic or metabolic origin, constitute "risk factors"for the wall of a blood vessel. We are here concerned with arterial hypertension, which is a primary risk factor for the production of atherosclerotic change. The SHR (spontaneously hypertensive rat) has been included among the more extensive series of experiments conducted by our research team (STAUBESAND et al.) as a particular model for the investigation of metabolic and hemodynamic "load-failure". The aims of the present contribution are to describe the morphological changes in the diseased vessel wall and to support these findings morphometrically.
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PMID:Ultrastructural and morphometric investigations into the arterial wall of the genetically hypertensive rat. 721 39

A part of the vasoconstrictor activity of angiotensin II (AII) may result from its ability to enhance norepinephrine (NE) release from sympathetic noradrenergic nerve terminals. To investigate this proposed pressor mechanism of AII, the effects of intravenous (i.v.) infusion of AII on blood pressure and plasma catecholamines in pithed rats were determined. Two naturally occurring angiotensins, valine5 AII (bovine) and isoleucine5 AII (rat), were administered in equal (72 ng/min) doses. Valine5 AII caused an 80% increase in mean arterial pressure (MAP) from 54 +/- 4 to 97 +/- 19 mm Hg. Isoleucine5 AII caused an 82% increase in MAP from 49 +/- 5 to 89 +/- 18 mm Hg. Neither angiotensin caused a change in heart rate, suggesting that pithing completely destroyed the central baroreceptor reflex mechanism. Plasma catecholamines were differentially affected by the peptides:isoleucine5 AII significantly increased plasma NE concentration by 82% compared to saline-infused rats (p less than 0.01). Valine5 AII did not significantly affect plasma NE concentration. Plasma dopamine and epinephrine concentrations were not significantly altered by infusion of either analog. Despite the significant increases in plasma NE concentrations with isoleucine5 in AII-infusion rats, there was no correlation between plateau MAP or the percent increase in MAP and plasma NE concentrations of individual animals within this group. The ability of angiotensin to elevate MAP, increase NE release from sympathetic nerve terminals, as well as potential differences in the actions of angiotensins in different species, and angiotensin receptor heterogeneity, are discussed.
Hypertension
PMID:Rat (Ile5) but not bovine (Val5) angiotensin raises plasma norepinephrine in rats. 729 41

1. A human urinary thermostable glycoprotein (ABG-TsU) believed to be a homologue of the plasma aldosterone-binding globulin (ABG) was isolated and purified by differential ultrafiltration, ion-exchange chromatography and gel filtration to electrophoretic homogeneity; it showed a charge heterogeneity in electrofocussing. 2. ABG-TsU was administered intraperitoneally to male rats in small daily doses (7 microgram/day per rat). Sustained hypertension developed in 5--8 days. 3. The treated rats showed no changes in plasma electrolytes, aldosterone or plasma renin activity; however, a significant increase in heart weight was observed. 4. This hypertension appears to be adrenal dependent since it is prevented by bilateral adrenalectomy or administration of an aldosterone antagonist, but not by adrenalectomy when aldosterone is given concomitantly with ABG-TsU.
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PMID:Experimental essential hypertension in the rat? 731 37

We investigated the possible central interaction of atrial natriuretic factor (ANF) and an endogenous Na+, K(+)-ATPase (Na-pump) inhibitor in normal rats. Release of an endogenous Na-pump inhibitor associated with deoxycorticosterone acetate-salt hypertension may be regulated in the anteroventral third ventricle (AV3V) area of the CNS. We reported earlier that bolus injection of synthetic 26-amino acid ANF (Arg101-Tyr126, 6 micrograms/250 g rat) into the lateral brain ventricle (ICV) promotes the appearance in the plasma of a Na-pump inhibitor in rats. To determine whether the AV3V area of the brain is involved in the ICV effect of ANF, we introduced electrolytic lesions in this area. This treatment abolished the appearance of the Na-pump inhibitor after intraventricular injection of ANF. To further localize the area and the pathways involved in the interaction of ANF and the Na-pump inhibitor, we produced bilateral medial coronal knife cuts designed to transect the medially coursing pathway through the periventricular tissue of the AV3V region between the level of the medial preoptic area and the anterior hypothalamic nuclei. These knife cuts also abolished the appearance of the Na-pump inhibitor after ICV injection of ANF. Our data to date indicate that centrally administered ANF promotes the appearance of a Na-pump inhibitor in the plasma. A central site of interaction between ANF and the Na-pump inhibitor appears to be the AV3V area and a medial pathway coursing caudally from the AV3V region.
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PMID:Effect of hypothalamic lesions on interaction of centrally administered ANF and the circulating sodium-pump inhibitor. 750 25

We investigated the effects of castration and testosterone propionate on tyrosine hydroxylase mRNA, its activity, and catecholamine synthesis in the adrenal medulla of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Four-week-old male rats were castrated. Testosterone propionate (500 micrograms per rat) was administered subcutaneously twice a week to castrated rats (between 14 and 25 weeks of age). Systolic pressure was measured at the age of 25 weeks, and rats were decapitated. The systolic pressure of castrated SHR was significantly lower than that of control and testosterone-replaced SHR. Epinephrine and norepinephrine levels, tyrosine hydroxylase activity, and tyrosine hydroxylase mRNA in the adrenal medulla of castrated SHR were significantly lower than in control and testosterone-replaced SHR. Systolic pressure and epinephrine and norepinephrine levels, tyrosine hydroxylase activity, and tyrosine hydroxylase mRNA levels in the adrenal medulla of WKY showed no significant differences among the control, castrated, and testosterone-replaced groups. These results suggest that androgens contribute to the development and maintenance of hypertension in SHR via sustained enhancement of tyrosine hydroxylase synthesis in the adrenal medulla, leading to increased epinephrine and norepinephrine levels.
Hypertension 1995 Jul
PMID:Influence of androgen on tyrosine hydroxylase mRNA in adrenal medulla of spontaneously hypertensive rats. 760 26

Arterial hypertension induced by microinjections of N-methyl-D-aspartate (NMDA) (2 nmol/rat) into the midbrain periaqueductal gray matter was used to assess the involvement of opioid receptors (mu, delta and kappa) in modulating pressor periaqueductal gray neurons. Groups (n = 5-8) of urethane-anaesthetised rats received, 5 min before NMDA, microinjections of selective opioid receptor antagonists in the periaqueductal gray area and arterial blood pressure was monitored. Pretreatments with naloxone (5 nmol/rat), a non selective mu receptor antagonist, or naltrindole hydrochloride (5 nmol/rat), a selective delta receptor antagonist, significantly (P < 0.05) decreased by 31% and 37%, respectively, NMDA-induced hypertension. The latency for the maximum increase of NMDA-induced hypertension was also significantly (P < 0.05) increased with naloxone. Pretreatment with nor-binaltorphimine (5 nmol/rat), a selective kappa receptor antagonist, only increased the latency of NMDA-induced hypertension. Each opioid antagonist failed per se to alter arterial blood pressure. Microinjection of morphine (13 nmol/rat), a non selective mu receptor agonist, significantly decreased (P < 0.05) by 57.5% NMDA-induced arterial hypertension and this effect was antagonised by naloxone. Combined pretreatments in the periaqueductal gray area with naloxone and the GABAA antagonist bicuculline (2.5 nmol/rat; 5 min before naloxone) antagonised the effect of naloxone on NMDA-induced hypertension. In contrast, bicuculline significantly (P < 0.05) potentiated morphine-induced decrease of NMDA hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of opioid receptors in N-methyl-D-aspartate-induced arterial hypertension in periaqueductal gray matter. 771 45

We investigated the effects of castration and testosterone propionate on sympathetic nervous systems in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Four-week-old male rats were castrated. For replacement of androgen, testosterone propionate (500 micrograms/rat) was administered subcutaneously 2 times a week to castrated rats after their 14th week. The systolic blood pressure of the castrated SHR (44 weeks) was significantly lower than those of intact SHR and testosterone-replaced SHR. The norepinephrine (NE) levels and the tyrosine hydroxylase (TH) activities in the abdominal aorta and mesenteric artery of castrated SHR (45-50 weeks) were significantly lower than those of intact SHR. The NE levels and the TH activities in these blood vessels of testosterone-replaced SHR recovered to the levels obtained in those of intact SHR. As well as the systolic blood pressure, the NE levels and TH activities in blood vessels of WKY were significantly lower than those of intact SHR and showed no significant difference among the three groups. These results suggest that androgen may contribute to the development of hypertension in SHR via sustained enhancement of TH activity in blood vessels leading to increased NE level.
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PMID:Possible involvement of androgen in increased norepinephrine synthesis in blood vessels of spontaneously hypertensive rats. 772 20


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