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

Urinary kallikrein was measured in rats bred to be susceptible (S) or resistant (R) to the hypertensive effect of salt. To determine kallikrein, three different methods were used: (1) a new direct radioimmunoassay (RIA) for the enzymic protein: (2) a method based on the capability of kallikrein, when incubated with kininogen, to generate kinins which were then measured by RIA (kininogenase activity); and (3) a method based on the capability of kallikrein to break the ester bond of p-tosyl-L-arginine methyl ester (HCl (TAMe). A significant correlation ( r = 0.90) was found between the direct RIA and the kininogenase method. It was found that urinary kallikrein was significantly decreased in the S as compared to the R rats by the use of these three methods. Urinary kallikrein in the S rats was much lower when measured by the kininogenase method than by direct RIA or esterolytic assay. This difference could be due to excretion of pre-kallikrein and/or kallikrein bound to an inhibitor (inactive kallikrein). It is suggested that the decrease of urinary kallikrein excretion (active and inactive) in the S rats could be a consequence of a genetic defect that may affect the development of hypertension perhaps through the alteration of sodium and water excretion by the kidney.
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PMID:Urinary kallikrein in rats bred for their susceptibility and resistance to the hypertensive effect of salt. A new radioimmunoassay for its direct determination. 63 96

The development of hypertension was studied in rats after neonatal sympathectomy by s.c. injection of 6-hydroxydopamine HCl. Three different types of hypertension were investigated: renal hypertension in the two-kidney Goldblatt model, steroid hypertension produced by deoxycorticosterone (DOCA) implantation and saline as drinking fluid, and genetic hypertension in the spontaneous hypertensive rat (SHR). Blood pressure was measured directly in conscious animals via the iliac artery. Mean blood pressure of conscious sympathectomized (SX) normotensive rats was not significantly different from that of normotensive controls. Renal hypertension reached the same level in controls and SX rats four weeks after application of a renal artery clip. DOCA-salt hypertension developed faster and to a higher level in SX rats than in control rats. The hypertension in SX DOCA-salt hypertensive rats was accompanied by a marked tachycardia. In contrast hypertension did not develop in SX SHR. Up to 12 months of age mean blood pressure was markedly lower than that of control SHR, but slightly higher than that of SX normotensive Wistar Kyoto rats. These differential effects of neonatal sympathectomy on the development of hypertension in the rat may point to differences in the pathophysiological mechanisms. It is concluded that an intact sympathetic nervous system is essential for the development of hypertension in SHR. In DOCA-salt hypertension the intact sympathetic nervous system appears to protect against a rapid rise in blood pressure.
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PMID:Differential development of renal, DOCA-salt, and spontaneous hypertension in the rat after neonatal sympathectomy. 75 48

1. Prolonged oral administration of NG-nitro-L-arginine (L-NNA) for a period of 5 weeks in 8 week old male normotensive Wistar-Kyoto (WKY) rats (n = 10), induced hypertension in all animals. Hypertension was characterized by a sharp initial increase in both systolic blood pressure (SBP) and mean blood pressure (MBP) until the third day (from 126 +/- 3 mmHg to 160 +/- 6 mmHg and from 95 +/- 3 mmHg to 133 +/- 6 mmHg, respectively). This was followed by a gradual and steady increase until the fourth week (163 +/- 4, 171 +/- 3 and 189 +/- 8 mmHg for SBP in weeks 1, 2 and 4, respectively; and 135 +/- 4, 143 +/- 3 and 157 +/- 5 mmHg for MBP in weeks 1, 2 and 4, respectively). 2. Intravenously L-arginine.HCl (500 mg/kg) administered on the last day of the 5th week abolished the effect of dietary L-NNA on the arterial blood pressure. 3. Dietary L-NNA-induced hypertension in WKY rats is easily obtainable and free of any surgical operation, and can be utilized as a new experimental model to further understand the importance of endothelium-dependent relaxing factor/nitric oxide in blood pressure regulation and to clarify the pathological significance in intact animals where endothelium-dependent relaxing factor/nitric oxide is functionally involved.
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PMID:Dietary NG-nitro-L-arginine induces sustained hypertension in normotensive Wistar-Kyoto rats. 152 64

The effects of the simultaneous steady-state intravenous infusion of benazeprilat, the active metabolite of benazepril HCl, and angiotensin I (AI) on mean arterial blood pressure were investigated in the conscious, unrestrained spontaneously hypertensive rat (SHR) and its normotensive parent strain, the Wistar-Kyoto (WKY) rat. A competitive inhibition model is applied and the limits of its validity are discussed. Deviations from the model are apparent at high drug infusion rates and may relate to the effect of benazeprilat on the clearance of AI. The strains differ in the amounts of angiotensin converting enzyme (ACE) or responsiveness to angiotensin II (AII), the drug clearances, and either the pharmacology or the distribution of the drug. Since the latter two differences are drug dependent, prediction between strains is rendered difficult. This steady-state approach relates the hypertension in the SHR to the amount of ACE or responsiveness to AII and renal function.
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PMID:Steady-state pharmacokinetics and pharmacodynamics of benazeprilat in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. 192 39

1. Cardiac output, arterial pressure, heart rate, systemic vascular conductance, respiratory rate and arterial blood PO2 and PCO2 were measured in unanaesthetized rabbits. Haemorrhage was simulated by inflating a cuff placed around the inferior vena cava so that cardiac output fell at a constant rate of about 8% of its resting value per min. 2. The effects of drug treatments on resting haemodynamic and respiratory variables, and on the haemodynamic response to simulated haemorrhage, were tested. The treatments were; 4th ventricular (-)-naloxone HCl (10-100 nmol), 4th ventricular H-Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (DAMGO; 30-300 pmol), and i.v. morphine sulphate (0.5-5.0 mumol kg-1). The interactions of graded 4th ventricular doses of naloxone (3-100 nmol) with the actions of DAMGO (100-300 pmol) on these responses were also assessed. 3. After sham treatments, the circulatory response to simulated haemorrhage had two phases. During the first compensatory phase, systemic vascular conductance fell, heart rate rose, and mean arterial pressure fell by only about 7 mmHg. A second decompensatory phase supervened when cardiac output had fallen by about 50%. At this point systemic vascular conductance rose abruptly and arterial pressure fell to less than or equal to 40 mmHg. 4. Low 4th ventricular doses of naloxone (10-30 nmol) and DAMGO (30-100 pmol) had no discernible effect on the circulatory response to simulated haemorrhage. Higher doses of naloxone (30-100 nmol) and DAMGO (100-300 pmol) prevented the decompensatory phase. These high doses of naloxone and DAMGO lowered resting heart rate without affecting the other haemodynamic or respiratory variables. 5. Low doses of i.v. morphine (0.5-1.Spumolkg-1) also had no discernible effect on the circulatory response to simulated haemorrhage. Higher doses of morphine (1.5-5.Opmol kg 1) abolished the decompensatory phase. These high doses caused respiratory depression without affecting the resting haemodynamic variables. 6. The prevention of circulatory decompensation by high doses of DAMGO was reversed by 3-10nmol of naloxone in 3 out of 4 rabbits and by 10-30 nmol of naloxone in all 4 rabbits. The decompensatory phase was, however, prevented by the combined high doses of DAMGO (100-300pmol) and naloxone (30-100 nmol). 7. These findings provide strong evidence that activation of mu-opioid receptors in the central nervous system abolishes circulatory decompensation during acute reduction of central blood volume in conscious rabbits. This effect does not appear to be due to activation of arterial chemoreceptors or to a non-specific increase in sympathetic vasoconstrictor drive, since respiratory depression and hypertension were not observed after 4th ventricular doses of DAMGO which abolished circulatory decompensation. Our results also provide indirect confirmation of our previous finding that naloxone acts to prevent circulatory decompensation by an antagonist action at central delta-receptors.
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PMID:Effects of mu-opioid receptor agonists on circulatory responses to simulated haemorrhage in conscious rabbits. 216 31

The effect of the selective 5-HT2 agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) on arterial pressure (AP), heart rate (HR), renal blood flow (RBF) and plasma renin activity (PRA) was determined in conscious rats. DOI increased AP and PRA, but decreased HR and RBF. All responses to DOI were abolished by central (LY 53857) or peripheral (xylamidine) 5-HT2 antagonists. Prazosin did not alter the AP or HR response to DOI. Chlorisondamine abolished the bradycardia but slightly increased the hypertension produced by DOI, while enalapril attenuated the pressor response. No further reduction was produced by the combination of enalapril and prazosin. Propranolol attenuated but did not eliminate the renin response, and blocked the bradycardia elicited by DOI. The data suggest that DOI activates 5-HT2 receptors located on vascular smooth muscle and/or the circumventricular organs of the brain to: (1) increase AP and reflexly decrease HR, (2) decrease RBF and (3) increase PRA. The hypertension is mediated by angiotensin II and direct vascular effects whereas the increase in PRA is mediated by an interaction of increased sympathetic nerve activity and decreased renal perfusion pressure.
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PMID:Hemodynamic and renin responses to (+-)-DOI, a selective 5-HT2 receptor agonist, in conscious rats. 218 26

We administered diltiazem HCl i.v. (0.05 mg/kg in bolus followed by 0.01 mg/kg/min for 45 min), and determined the changes in blood pressure (BP), glomerular filtration rate (GFR), renal blood flow (RBF), total renal resistance, urinary volume (UV), urinary sodium (UNa) and potassium excretion, urea and osmolar clearance, and tubular reabsorption ratio of sodium (TRNa%). The serum concentration of diltiazem achieved was similar to the maximum level after a single oral dose of 120 mg. GFR and RBF were measured by i.v. infusion of sodium thiosulfate and sodium rho-amino-hippurate, respectively, as indicators. The subjects included 12 cases of essential hypertension (EH), 10 of chronic glomerular nephritis (CGN) with hypertension, 12 of CGN without hypertension, 12 of ischemic heart disease (IHD), and 10 of normotensive controls. BP decreased in hypertensives but not in normotensives. In patients with EH, GFR and RBF increased markedly (by 25.3 +/- 33.8% and 30.7 +/- 39.5%, respectively). In patients with IHD, GFR increased slightly by 9.8 +/- 17.6%, whereas in patients with CGN with hypertension, GFR decreased by -4.3 +/- 14.3%. No significant change of these indices was observed in normal subjects and in patients with CGN without hypertension. UV and UNa increased and TRNa% decreased in all groups. Urea and osmolar clearance increased in almost every group.
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PMID:Clinical effects of intravenous diltiazem hydrochloride on renal hemodynamics. 243 98

The interaction of the vasoconstrictor peptide, endothelin-1 (ET-1), and the endothelium-derived vasodilator eicosanoid, prostacyclin, was examined as it pertains to the modulation of gastric mucosal integrity. Using an ex vivo chamber preparation of the rat stomach, the effects of intravenous ET-1 on the susceptibility of the mucosa to damage induced by topical application of an irritant, 20% ethanol, were examined. ET-1 significantly augmented gastric hemorrhagic damage induced by the irritant when administered at concentrations in the 10(-7) to 10(-6) M range. Pretreatment with indomethacin at a dose that inhibited gastric prostacyclin synthesis by over 85% resulted in significant augmentation of the ulcerogenic actions of ET-1. The damaging actions of ET-1 could be significantly reduced by topical pretreatment of the gastric mucosa with prostacyclin (5-50 micrograms/ml). This pretreatment also significantly reduced the hypertension and hemoconcentration observed following ET-1 administration. ET-1 also significantly augmented the susceptibility of the gastric mucosa to injury induced by hydrochloric acid. Oral administration of 150 mM HCl produced little or no gastric damage in control rats. However, a 5-min intravenous infusion of ET-1 produced significant increases in the severity of acid-induced gastric damage in a concentration-dependent manner (10(-7) to 10(-6) M). These results demonstrate that ET-1 is a potent ulcerogenic agent in the rat stomach. The ulcerogenic actions of ET-1 can be significantly reduced by prostacyclin, suggesting that the balance between endothelial cell release of ET-1 and prostacyclin may be an important factor in modulating gastric mucosal integrity.
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PMID:The modulation of gastric mucosal integrity by endothelin-1 and prostacyclin. 247 84

Magnesium therapy has been shown, by us, to attenuate monocrotaline (MCT)-induced pulmonary artery hypertension (PAH), right ventricular hypertrophy and pathological changes in the pulmonary vasculature in 75% of Sprague-Dawley rats. We studied Wistar rats to determine if there was a strain difference in response to MCT and magnesium therapy. Wistar rats were given 60 mg/kg of MCT and studied 3 weeks later, following a protocol similar to that for Sprague-Dawley rats. There was 100% mortality in Wistar rats weighing less than 230 g. The mortality rate in Sprague-Dawley rats of a similar weight range was significantly less (15%). With 40 mg/kg of MCT, Wistar rats developed pulmonary hypertension and right ventricular hypertrophy comparable to those seen in Sprague-Dawley rats administered 60 mg/kg MCT. The percent weight gain over a 3-week period was significantly higher in the Wistar control group than that in the Sprague-Dawley controls (61 vs. 39%; p less than 0.05). Oral magnesium therapy (magnesium aspartate HCl) attenuated pulmonary hypertension and right ventricular hypertrophy in 100% of the Wistar rats studied. A group of Sprague-Dawley rats was given 40 mg/kg of MCT and studied 3 weeks later. PAH and right ventricular hypertrophy in this group were not significantly different from the rats of the same strain injected with the higher dose of MCT. In conclusion, faster growing rats (Wistar) appear to be more sensitive to MCT. Both strains show a significant attenuation of cardiopulmonary changes induced by MCT when treated with oral magnesium.
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PMID:Strain differences in pulmonary hypertensive response to monocrotaline alkaloid and the beneficial effect of oral magnesium treatment. 252 10

Preparations of beta-blockers, propranolol-HCl and atenolol, in poly(vinyl alcohol) (PVA) hydrogel were designed for the therapeutic treatment of hypertension by transrectal delivery. In vitro release characteristics and plasma drug concentration profiles after rectal administration in rats and dogs were examined. The PVA hydrogels containing beta-blockers were prepared by a low-temperature crystallization method. The release of beta-blockers from hydrogel preparations was consistent with Fickian diffusion (Higuchi model); the drug release versus the square root of release time profile gave a straight line over 60% of the total release process. The release of beta-blockers from hydrogel preparations increased at higher concentrations of PVA in the hydrogel preparations and was not affected by the pH of hydrogel preparations. Plasma concentrations of beta-blockers after rectal administration of hydrogels were higher than those after administration of suppositories (Witepsol H-15) in rats and dogs. The drug plasma concentrations increased at higher concentrations of PVA in hydrogel preparations. In the case of propranolol, which is a hepatic high-clearance drug, area under the blood concentration curve, 0-8 h after rectal administration of a hydrogel preparation (20% w/w PVA, pH 7.0) was 2.16 times and 5.26 times higher than those obtained with Witepsol H-15 suppository and oral administration, respectively. Rectal administration with PVA hydrogels is a favorable route for a hepatic high-clearance drug such as propranolol.
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PMID:Design of polyvinyl alcohol hydrogel as a controlled-release vehicle for rectal administration of dl-propranolol-HCl and atenolol. 260 98


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