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

A new system is proposed for treating the spectrum of patients with high blood pressure. It is based on studies of the renin axis using renin profiling, pharmacologic probes and our bipolar vasoconstriction-volume hypothesis. The new system does not require renin profiling, pharmacologic testing or a vasoconstriction-volume analysis for widespread application. But these procedures, whenever available, will make treatment more efficient and more certain, and at the same time provide better base line definition. In the new system, all patients, except the elderly and those with congestive heart failure, bradycardia or a history of asthma, are treated first with propranolol alone, a procedure which will diminish or normalize blood pressure in many patients with high and noraml renin levels. For nonresponders, diuretic therapy is then superimposed. Subsequently, a propranolol subtraction trial picks out the low-renin patients who will usually respond to a diuretic alone. This program is likely to be fully effective in possible up to 85 per cent of patients. For the residual smaller fraction, drugs such as hydralazine, methyl DOPA, clonidine, reserpine or guanethidine are then added in traditional trial and error fashion. The proposed system has the theoretic attraction for long-term commitment, implicit in antihypertensive therapy, of achieving blood pressure control in large fractions with one drug instead of two or with two drugs instead of three or more. Moreover, the large groups who respond to therapy with propranolol alone (most high-renin and normal-renin patients) or to diuretics alone (most low-renin patients) gain the advantage of simple, more specific, long-term (i.e., antirenin or antivolume) therapy. The use of propranolol alone has practical and theoretic advantages over diuretics. Control may be achieved with even fewer side effects and without hypokalemia and chronic dehydration with its possibly adverse consequences (hyperuricemia, azotemia, hyperlipidemia, hyperreninemia, increased blood viscosity). Also, propranolol provides more direct control of the increased peripheral resistance and of neurogenically-induced swings in blood pressure. At the same time, the new system efficiently exploits the long-term use of diuretic therapy alone in low-renin patients in whom volume excess seems a causal factor. And it tends to avoid the use of diuretics in high-renin patients and of beta-blockers in low-renin patients in whom these drug types may be contraindicated.
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PMID:Modern system for treating high blood pressure based on renin profiling and vasoconstriction-volume analysis: a primary role for beta blocking drugs such as propranolol. 1 Jul 30

A hypothalamic role in the aetiology of hypertension in the spontaneously hypertensive rat (SHR) has been suggested by prior observations. In an attempt to determine whether the central control of prolactin (PRL) release is altered in the SHR we have compared the PRL response to immobilization stress, thyrotrophin releasing hormone (TRH), haloperidol, and L-DOPA in the SHR and in normotensive Wistar control rats. Carotid artery catheters were inserted 48 h prior to the PRL response studies and the catheters were maintained patent with heparinized saline. Timed blood samples were obtained in SHR and control rats weighing 180-225 g. The SHR demonstrated elevated basal serum levels of PRL and greater PRL responses to stress. However, administration of L-DOPA resulted in a similar suppression of serum PRL in the SHR and in the normotensive controls. These findings suggest alteration in the central control of PRL release in the SHR. Observations of elevated basal PRL, exaggerated PRL in response to L-DOPA in SHR are consistent with normal pituitary responsiveness to dopamine suppression of PRL release, but defective hypothalamic metabolism of dopamine. Alterations in central dopamine control mechanisms in the SHR may play a role in the pathogenesis of essential hypertension in these animals.
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PMID:Hyperprolactinaemia in the spontaneously hypertensive rat. 10 13

We examined the effect of L-Dopa, after peripheral L-amino acid decarboxylase inhibition, on sympathetic nerve activity (SNA) and blood pressure in spontaneously hypertensive rats (SHR) and in normotensive control rats. L-Dopa reduced SNA in both groups of animals. The SHRs were significantly more sensitive to the depressor effect of L-dopa than were the control animals, the threshold dose for reduction of SNA being 3 mg/kg in the SHR and 15 mg/kg in control rats. Similarly, the magnitude of inhibition of SNA was substantially greater in the SHR than in normotensive rats. The reduction in SNA in the SHR accompanied by a parallel fall in blood pressure. In contrast, blood pressure in control rats did not change significantly, even though SNA was diminished. Studies of the penetration of L-dopa into the cerebral parenchyma revealed that equivalent amounts of the amino acid entered the brains of the two groups of rats. These results suggest that the SHRs are more sensitive to the SNA-inhibiting effects of L-dopa than are normotensive rats. In addition, they confirm our previous suggestion that excessive SNA plays a causative role in the hypertension of the SHR.
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PMID:Effect of l-dopa on sympathetic nerve activity and blood pressure in the spontaneously hypertensive rat. 65 56

Administration of 1-DOPA into healthy persons increased its excretion with urine and elevated the adrenaline secretion. The increase of catecholamines excretion was not observed in aged patients with hypertension; the data obtained suggest that the synthesis of catecholamines with utilization of DOPA was inhibited. In patients with ulcerous disease excretion of 1-DOPA was not increased after its administration, but secretion of catecholamines was decreased during the day time. Under ulcerous disease 1-DOPA appears to be used in process unrelated to synthesis of catecholamines.
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PMID:[L-DOPA test for evaluating in vivo catecholamine biosynthesis in normal persons and persons with different diseases]. 88 97

Tests conducted on anesthetized rats with experimental renal hypertension demonstrated that octadine, reserpine and methyl-DOPA with their one-time administration produce at the onset of the maximal hypotensine effect of fall of the arterial pressure at the expense of the lowered total peripheral resistance. Most characteristic of the action exercised by these drugs is an increased fraction of the cardiac ejection going to the gestro-intestinal tract. In hypertension all the substances under study reduce the coronary and splenic fractions of the cardiac ejection. Reserpine and methyl-DOPA do not change, while octadine reduces the fraction of the cardiac ejection that goes to the kidney.
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PMID:[Effect of reserpine, octadine and methyldopa on the distribution of cardiac output in hypertension]. 102 83

Keeping in mind the vasodilator action of prostaglandins, the control that they exercise over the vascular supply of kidneys and the sympathetic activity, research was conducted in order to establish the effect of arachidonic acid, the precursor of PGE2, on experimental hypertension in the rat. The experimental hypertension was induced by unilateral nephrectomy, followed by the administration of DOCA and the elevated sodium diet. The treatment was short in one group, long in the other, and both groups were compared to a control hypertensive group which received no treatment at all. Arachidonic acid worsened the experimental hypertension by 37% in the long treatment, and by 25% in the short treatment. The administration of lysine-acetylsalicylate diminished this hypertension. A non-saturated acid, oleic acid, which is not involved in prostaglandin synthesis, has no action. The authors would like to emphasize that in one of the previous experiments, L-tyrosine, the precursor of catecholamines, diminished the experimental hypertension in the rat, and also that L-DOPA and IMAO (MAOI) have comparable effects. It seems, therefore, that the depression of the central catecholaminergic activity, which is supposed to be the action of arachidonic acid via an increase in the PGE2 synthesis, appears to increase hypertension. It is noteworthy that the medial forebrain bundle (MFB) is catecholaminergic and that the periventricular system (PVS) is cholinergic. Thus hypertension may represent the peripheral vascular response to anguish which results from the activation of PVS and from the depression of MFB.
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PMID:The action of arachidonic acid on experimental hypertension in the rat. 112 60

Biogenic amine metabolism may be altered in hypertension and thus contribute to its pathophysiology. This report describes an abnormality in dopamine excretion in hypertensive subjects in the postabsorptive state that persists despite an increase in dietary precursors for dopamine supplied by a protein meal. We studied seven normotensive and six nonmedicated hypertensive men after two different meals: 60 g protein and a noncaloric electrolyte-equivalent broth. Overall mean sodium excretion was 56% higher in the hypertensive group throughout both meal studies (p less than 0.01), implying higher chronic dietary sodium intake. Despite this, overall urinary excretion of dopamine tended to be lower in hypertensive than in normotensive subjects (p = 0.06). Hypertensive also differed from normotensive subjects in their response to protein feeding. In the normotensive subjects there was a 23% increase in urinary dopamine excretion (p less than 0.05), which was not seen after the noncaloric meal. In the hypertensive subjects, there was no change in urinary dopamine after the protein meal. In the normotensive subjects there was a 74% increase in sodium excretion (p less than 0.01) after the protein meal, but no significant change was seen in the hypertensive subjects. There were no differences in baseline renal plasma flow or glomerular filtration rate between the groups and no statistically significant differences between the groups in their renal hemodynamic responses to the meals. In summary, hypertensive subjects have less renal dopamine production for the amount of sodium ingested and a decreased renal dopamine production in response to a protein load as compared with normotensive subjects, consistent with a renal defect in conversion of DOPA to dopamine.
Hypertension 1992 Jun
PMID:Altered dopaminergic responses in hypertension. 159 53

This study investigates the function of the hypothalamic-pituitary-adrenocortical system (HPAS) in adult rats with inherited stress-induced arterial hypertension (ISIAH rats) whose arterial blood pressure was lowered by the dopamine precursor L-DOPA treatment during early development (on days 21-25 of life). The response of the HPAS induced by emotional stress was significantly lower in intact ISIAH rats than in normotensive Wistar animals. Injections of L-DOPA on days 21-23 or 21-25 of postnatal life were followed by a long-lasting complete restoration of the emotional stress response in adult ISIAH rats. The restoring effect of L-DOPA was produced through enhancement of synthesis of the brain noradrenaline and, perhaps, adrenaline. The effect was associated with a normalization of the response of the brain adrenergic system to noradrenaline and did not relate to an increase of the plasma corticosterone level after L-DOPA administration in early ontogeny.
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PMID:Treatment with L-dopa in early life restored pituitary-adrenocortical response to emotional stress in adult rats with inherited arterial hypertension. 185 49

Dopamine in urine is derived substantially from renal uptake and decarboxylation of 3,4-dihydroxyphenylalanine (dopa), and increases in excretion of dopa normally parallel increases in excretion of dopamine during salt loading. Since patients with salt-sensitive hypertension may have decreased urinary excretion of dopamine during dietary salt loading, the present study was designed to evaluate the response of dopa to salt loading. Sixteen inpatients with normal-renin essential hypertension ate a constant metabolic diet containing 9 mmol/day sodium for 7 days, followed by the same diet but containing 249 mmol/day sodium for 7 days. Salt sensitivity was defined as an increase in mean arterial pressure of 8 mm Hg between the diets; on this basis, nine patients were salt-sensitive and seven, salt-resistant. The rate of urinary dopa excretion was significantly higher in the salt-sensitive patients throughout the study (mean rates 132 +/- 13 nmol/day in the salt-sensitive group and 78 +/- 9 nmol/day in the salt-resistant group for the 14 days of observation, p less than 0.01). When dietary sodium intake was increased to 249 mmol/day, urinary dopa excretion increased significantly more in salt-sensitive patients than salt-resistant patients. At the end of the high salt diet, dopamine excretion was significantly attenuated in the salt-sensitive patients, despite higher rates of dopa excretion. Thus, the urinary ratio of dopamine to dopa was decreased in salt-sensitive patients, regardless of salt intake.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Nov
PMID:High urinary dopa and low urinary dopamine-to-dopa ratio in salt-sensitive hypertension. 193 64

Dopamine (DA), via DA-1 receptors, regulates Na+ transport in the kidneys. Dopamine is synthesized from L-DOPA in the proximal tubule and presumably secreted as an autocrine/paracrine substance to stimulate DA-1 receptors localized on proximal tubular cells. We have previously reported the presence of DA-1 receptors in renal cortical homogenates and on the isolated proximal tubule of the rat and rabbit, consistent with the dopamine autocrine/paracrine model. We have localized DA-1 receptors in the proximal straight tubule of the rabbit, and in the cortical collecting duct of the rabbit and rat, but not in the distal collecting tubule or the cortical thick ascending loop of Henle. The presence of functional DA-1 receptors has been substantiated by the coexistence of DA-1 agonist-stimulated adenylate cyclase activity in the same nephron segments in which DA-r receptors have been found. Increased concentrations of intrarenal dopamine induced by dopamine-beta-hydroxylase inhibition with SKF-102698 caused a down regulation of proximal tubular DA-1 receptors and almost complete ablation of DA-1 agonist stimulated adenylate cyclase activity. Thus, dopamine may play a role in the regulation of DA-1 receptors and their linkage with adenylate cyclase. Since alterations in the renal dopaminergic system have been measured in some forms of experimental hypertension, we studied DA-1 receptors and their coupling to adenylate cyclase in the spontaneously hypertensive rat (SHR).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A renal dopamine-1 receptor defect in two genetic models of hypertension. 197 47


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