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

The pharmacological properties of 2-(2-chloro-p-toluidino)-2-imidazoline-nitrate (tolonidine) a new synthetic derivative of imidazoline are reported in a series of three successive articles. This compound has been shown to possess hypotensive and antihypertensive properties. After i.v. administration, the hypotensive phase was preceded by hypertension related to the potent direct alpha-sympatheticomimetic properties of the product. This pressor response, which was not seen after oral administration, was accompanied by a marked decrease in cardiac output and a significant increase in peripheral vascular resistance. The hypotensive action of the product was due to a drop in cardiac output probably reinforced by a decrease in vasoconstrictor sympathetic tone due to a central action. Whatever the route of administration, tolonidine slowed heart rate independently of blood pressure variations, due essentially to an increase in vagal tone. In studies of diuresis, liquid and salt loss were observed in the cat, not in the dog. At doses which induce a drop in blood pressure tolonidine did not produce a reduction in pilocarpine-induced salivary secretion and only partially inhibited gastric secretion. In the central nervous system, tolonidine produced a sedation which first appeared at doses having an antihypertensive effect but which was only fully apparent with increased doses. A decrease in the release of cerebral amines, serotonin and noradrenaline by tolonidine is proposed. Tolonidine was compared with three other antihypertensive agents: clonidine, which is structurally related, and guanethidine and mecamylamine, which are structurally unrelated and have a different mode of action. A close resemblance of the pharmacological properties of tolonidine and clonidine was established due to the chemical relationship between the two substances.
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PMID:Pharmacological properties of 2-(2-chloro-p-toluidino)-2-imidazoline-nitrate (tolonidine), a new antihypertensive agent. III. Action on the secretions of the digestive tract and on the central nervous system, acute toxicity. 0 86

Present knowledge of the mechanisms regulating release of renin is reviewed with particular emphasis on neural factors. Evidence is given for a direct effect of renal innervation on beta adrenergic receptors in juxtaglomerular cells, and for the involvement of reflex release of renin in conditions such as tilting and acute salt depletion. Participation of neural and nonneural mechanisms of control is also shown to occur in other conditions, such as aortic constriction and hemorrhage. The view is held that neural sympathetic factors might explain some of the renin disturbances found in essential hypertension. First, in patients with high renin hypertension part of the hypertension is renin-dependent, and these pressor levels of renin seem to be neurally induced since they can commonly be suppressed by beta adrenoreceptor blocking agents. Second, the hypothesis is presented that patients with low renin hypertension, at least those who have no volume disturbance, have a blunted sympathetic control of renin release. Therefore a sufficiently precise test of sympathetic activity, and possibly of body fluid volumes, should be associated with renin profiles for a better understanding of the pathophysiology of arterial hypertension and as a better guide to therapeutic management. Indeed, most of the available antihypertensive drugs act on sympathetic activity, body fluid volume or renin, and this multifaceted profile would provide more rational guidelines for treatment.
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PMID:Control of renin release: a review of experimental evidence and clinical implications. 0 64

The hypertension induced in adult male rats by doca/salt was found to be accompanied by a significant rise in whole brain tyrosine hydroxylase (TH) activity. A smaller hypertensive effect, produced by angiotensin (750 ng kg-1 daily) was also accompanied by a proportional rise in whole brain TH activity. The specific antagonists spironolactone and saralasin completely blocked both responses in the doca/salt- and angiotensin-treated animals respectively and spironolactone showed a partial inhibition of the effects of angiotensin. In all the animals treated there was a clear correlation between systolic blood pressure and whole brain TH activity. The significance of these changes is discussed in the light of the central mechanism of hypertension.
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PMID:Brain tyrosine hydroxylase activity and systolic blood pressure in rats treated with either deoxycorticosterone and salt or angiotensin. 0 9

1. Activity of peripheral and central catecholaminergic neurons was studied in spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats. 2. In young SHR (4 weeks) the plasma values of bpth noradrenaline and dopamine-beta-hydroxylase activity were increased compared with those of normotensive rats of the Wistar/Kyoto strain. Total catecholamines (mostly adrenaline) were not significantly different. 3. In the adrenal glands of 2-weeks-old and 4-weeks-old SHR activities of tyrosine hydroxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyl transferase were decreased, compared to Wistar/Kyoto rats. 4. The adrenaline-forming enzyme was elevated in the A1 and A2 regions of the brain stem of 4-weeks-old SHR and in the A1 region of adult DOCA-salt hypertensive rats. 5. In the adrenal glands of adult DOCA-salt hypertensive rats tyrosine hydroxylase activity was increased. 6. These results implicate peripheral noradrenaline-containing neurons and central adrenaline-containing neurons in the development of genetic and experimental hypertension in rats.
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PMID:Peripheral and central catecholaminergic neurons in genetic and experimental hypertension in rats. 1 56

The activities of monoamine biosynthetic enzymes were measured in brain regions of several hypertensive rat models at various ages. The types of hypertensive rats were the spontaneously hypertensive rat (SHR) and a stroke-prone substrain of the SHR as well as DOCA-salt and renal hypertensive rats. The genetically hypertensive rats had significantly elevated blood pressures as compared to the Wistar-Kyoto control rat after 5 weeks of age. During the early development of hypertension in the SHR, the activities of tyrosine hydroxylase in the hypothalamus and corpus striatum and of dopamine-beta-hydroxylase in the hypothalamus and pons-medulla were significantly higher than in the control rats. Tryptophan-hydroxylase was also elevated in the hypothalamus in SHR. From 3 to 8 weeks of age there appeared to be a significant correlation between hypothalamic dopamine-beta-hydroxylase activity and blood pressure in the hypertensive rats. In contrast, the activities of tyrosine hydroxylase and dopamine-beta-hydroxylase were slightly decreased in the DOCA-salt and renal hypertensive rats. It is suggested that noradrenergic or adrenergic neurons in the hypothalamus may participate in the initiation of elevated blood pressure in the genetic, but not in the DOCA-salt or renal hypertensive rats.
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PMID:Regional changes in the activities of aminergic biosynthetic enzymes in the brains of hypertensive rats. 1 54

The activity of lysyl oxidase which catalyzes the initial step of cross-linking of collagen and elastin polypeptides was measured in blood vessels of the hypertensive rat. The enzyme activity was increased in the aorta and mesenteric artery when hypertension was induced in 8-week-old rats with administration of deoxycorticosterone acetate (DOCA) and 1% saline. Reserpine diminished this increase in vascular lysyl oxidase activity concomitant with reduction in blood pressure. When beta-aminopropionitrile, a specific inhibitor of lysyl oxidase, was administered before the onset of DOCA-salt hypertension, the aortic collagen content was reduced markedly. Concomitant with reduction in the aortic collagen content, the development of hypertension and arteriosclerotic changes in the kidney was partially prevented. These results would indicate that hypertension increases the amount and the degree of cross-linking of vascular collagen and that the deposition of excess collagen in the vascular wall contributes to the development of hypertension and arteriosclerosis.
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PMID:Increased lysyl oxidase activity in blood vessels of hypertensive rats and effect of beta-aminopropionitrile on arteriosclerosis. 2 27

Prevention of complications of hypertension requires the lowering of blood pressure. The therapeutic goal is to achieve and maintain a diastolic pressure of less than 90 mm Hg with minimal adverse effects. The treatment of patients with established diastolic blood pressures between 90 and 104 mm Hg (determined from three separate readings) should be individualized; general measures such as weight loss and salt restriction should be tried first as an alternative to drug therapy. Patients with diastolic pressure in excess of 104 mm Hg should be treated with antihypertensive drugs; the first step should be the use of a thiazide diuretic in addition to general measures. Patients with diastolic pressures of 90 to 115 mm Hg may require the addition of a beta-adrenergic-receptor antagonist, methyldopa or clonidine if the therapeutic goal is not achieved; rarely they require the further addition of hydralazine or prazosin. Patients with diastolic pressures of 116 to 129 mm Hg usually require initially both a thiazide diuretic and a beta-blocker, methyldopa or clonidine; if the therapeutic goal is not achieved, hydralazine or prazosin is added, and if a further hypotensive effect is required guanethidine can be added. Patients with severe hypertension (diastolic pressures greater than 130 mm Hg) may require urgent treatment with combinations of drugs of all three levels. Emphasis should be placed on individualized therapy and patient compliance in the assessment of therapeutic failures. These "step-care" guidlines represent a framework for antihypertensive therapy devised from information available in 1977. It is not a rigid scheme and should be adjusted to the individual patient to ensure as normal a life as possible.
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PMID:Approach to drug therapy for hypertension. 3 78

1. Chronic hypertension was induced in Wistar rats with intact kidneys by subcutaneous implantation of 50 mg of deoxycorticosterone acetate (DOCA) in wax and addition of sodium chloride (9 g/l) to the drinking water. 2. The development of DOCA/salt hypertension, as monitored by tail-cuff plethysmography, was prevented by: (a) destruction of the peripheral adrenergic nerves with neonatal administration of guanethidine (80 mg/kg subcutaneously for the first 14 days postnatally); (b) bilateral stellate ganglionectomy; (c) oral administration of the beta-adrenoreceptor antagonists propranolol or atenolol (1 mg day-1 kg-1) during the period of DOCA/salt treatment. 3. The dose of DOCA used was sufficient to inhibit the atrial Uptake2 pathway completely: this process appears to participate in termination of action of neurally released noradrenaline in the heart. 4. It is suggested that this model of DOCA/salt hypertension is due to adrenergic enhancement of cardiac output in the presence of an increased sodium load. The enhancement may be partly due to deficient myocardial inactivation of noradrenaline.
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PMID:Dependence of deoxycorticosterone/salt hypertension in the rat on the activity of adrenergic cardiac nerves. 3 42

We wish to determine what cellular and functional alterations are associated with the development of glomeruloscierosis when rats with one kidney are fed an excess of salt or protein. Rats with one kidney are more likely to develop pronteinuria and glomerulosclerosis than control animals. Blood pressure recordings indicate that proteinuria and glomerulosclerosis occur before hypertension is evident. Fluorescent antibody studies disclose that albumin accumulates in the epithelial cells of glomeruli and tubules. Ultrastructural examination shows that vacuolozation of epithelial cells and basement membrane thickening precede the sclerotic collapse of capillary loops. Increased concentrations of sodium or urea that are found in urines of these rats favor the point of view that an elevation of solute load when combined with a reduction of renal mass will on some unknown manner accelerate the deterioration of glomeruli.
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PMID:Protein overload nephropathy in rats with unilateral nephrectomy. A correlative light immunogluorescence and electron microscopical analysis. 4 49

The effect of infusion of the angiotensin II antagonist P113 on blood-pressure (B.P.) has been studied in 10 patients with various forms of hypertension under four different conditions: before and after salt depletion and with or without propranolol treatment. The fall in B.P. after P113 infusion significantly correlated with log P.R.A. (plasma-renin activity), irrespective of diagnosis or treatment. P113 infusion caused a consistent fall in B.P. only after sodium depletion. The changes in B.P. after P113 infusion and those induced by propranolol correlated only during sodium depletion, when P.R.A. values rose. It is concluded that sodium depletion induced "renin dependency" of B.P. in all patients. The decrease in B.P. renin dependency after propranolol therapy suggests that suppression of P.R.A. is one of the antihypertensive mechanisms underlying the action of this drug.
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PMID:Renin dependency of blood-pressure. Analysis by angiotensin II antagonist P113 in hypertensive patients treated with salt depletion and propranolol. 5 53


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