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

The dopamine beta-hydroxylase inhibitor SK&F 102698 was characterized by studying its cardiovascular effects in hypertensive rats. The antihypertensive effects of SK&F 102698 (50 mg/kg p.o.) were studied in three different rat models of hypertension. In spontaneously hypertensive and deoxycorticosterone acetate-salt rats SK&F 102698 produced blood pressure reductions of approximately 21 and 23%, respectively. In contrast, SK&F 102698 did not produce a significant decrease in blood pressure in 2-kidney, 1-clip Goldblatt hypertensive rats. The antihypertensive mechanism of action of dopamine beta-hydroxylase inhibition was probed with the selective DA1-receptor antagonist SCH 23390, which produced an attenuation of the antihypertensive effects of SK&F 102698. Experiments were designed to separate the peripheral from the central components of the cardiovascular effects of SK&F 102698. In spinal cord stimulated pithed spontaneously hypertensive rats, SK&F 102698 reduced blood pressure but not heart rate, indicating a peripherally mediated vasodilation and a centrally mediated heart rate effect. Furthermore, when SK&F 102698 was administered directly into the fourth ventricle of conscious spontaneously hypertensive rats, a pronounced bradycardia and lowering of blood pressure was observed. SCH 23390 (200 micrograms/kg i.v.) and l-sulpiride (1 mg/kg i.v.) inhibited the cardiovascular effects of SK&F 102698 administered into the fourth ventricle. These data indicate that inhibition of dopamine beta-hydroxylase with SK&F 102698 results in both peripherally and centrally mediated cardiovascular effects and suggest that central dopamine receptors contribute to the control of systemic blood pressure in hypertensive models associated with an increased sympathetic outflow.
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PMID:Further characterization of the cardiovascular effects of the dopamine beta-hydroxylase inhibitor SK&F 102698 in conscious hypertensive rats. 305 29

Dopamine (DA) receptors have been divided into two subtypes: DA1 receptors which subserve vasodilation in renal, mesenteric, coronary, and cerebral vascular beds, and DA2 receptors which when activated cause inhibition of release of norepinephrine in sympathetic nerve endings. The subdivisions were made on the basis of differences in chemical structure and potency series of agonists and antagonists for the two receptor subtypes. Agonists and antagonists are now available which selectively act on DA1 or DA2 receptors. The clinical use of DA, DA pro-drugs, and selective DA agonists is discussed with particular emphasis on the treatment of congestive heart failure and hypertension. Finally, data are presented concerning possible relationships between peripheral DA1 and DA2 receptors and DA receptors classified in the central nervous system.
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PMID:Dopamine: receptors and clinical applications. 315 32

Bromocriptine and co-dergocrine (Hydergine R) reduce blood pressure and heart rate in experimental animals largely by stimulating DA2 receptors. A stimulant effect on DA1 receptors can be demonstrated in isolated tissues, but this action does not appear to make an important contribution to the depressor response to the two compounds, since effects are abolished by DA2 receptor blockade. Although both compounds are known to penetrate the brain, their antihypertensive effects, and the concomitant reductions in plasma noradrenaline levels produced in hypertensive patients can be prevented by domperidone, confirming a peripheral site of action. A review of the data available concerning the cardiovascular effects of bromocriptine and co-dergocrine in animals and man suggests that a DA2 receptor stimulant is effective in the treatment of hypertension.
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PMID:Is stimulation of prejunctional dopamine receptors an antihypertensive principle? 330 28

It is controversial whether dopamine (DA) is a peripheral neurotransmitter in the cardiovascular/renal system. The endogenous concentration of DA in the heart and blood vessels is generally only a fraction (5%) of that of norepinephrine (NE). With perhaps the exception of the kidney, the majority of the evidence suggests a precursor role for this amine rather than that of a neurotransmitter. The main weakness of arguments favoring DA as a vascular neurotransmitter is relative lack of data showing selective DA release and lack of effects of selective DA antagonists on neural stimulation. However, DA receptors have been characterized in cardiovascular tissues and are of two types: DA1 receptors located on vascular smooth muscle (postjunctional), which appear to mediate relaxation of the muscle, and DA2 receptors located on sympathetic nerves (pejunctional), which inhibit NE release. These receptors are interesting and potential target sites for novel cardiovascular drug action for the treatment of hypertension and renal ischemia. Moreover, selective DA receptor agonists will be important tools in understanding the role of DA receptors in normal and disease states.
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PMID:Dopamine and dopamine receptors as target sites for cardiovascular drug action. 613 21

Intravenous (i.v.) infusions of SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7- ol) produced dose-related antagonism of dopamine (DA)-induced renal vasodilation in phenoxybenzamine-treated dogs at infusion rates of 0.05, 0.15, and 0.5 microgram/kg/min. The highest rate of infusion, 0.5 microgram/kg/min, resulted in pronounced antagonism of this DA1-receptor-mediated response. In contrast, a 10 times higher infusion rate, 5 micrograms/kg/min, did not antagonize the following DA2-mediated responses: increase in femoral blood flow produced by apomorphine and piribedil in untreated dogs; and N,N-di-n-propyl DA (DPDA)-induced inhibition of the tachycardia produced by cardiac accelerator nerve stimulation. Infusions of 0.5 micrograms/kg/min or greater of SCH 23390 did not affect the actions of agonists of alpha1-, alpha2-, beta1-, and beta2-adrenergic, histamine, serotonin, and cholinergic receptors, or the vasodilation produced by bradykinin. At the infusion rates used in these studies, SCH 23390 did not affect arterial blood pressure or heart rate. These data indicate that SCH 23390 is the most specific and selective antagonist of DA1 receptors thus far described. Accordingly, SCH 23390 should be extremely useful in investigations of potential physiological and pathological roles of DA and in the classification of DA receptors.
Hypertension
PMID:Separation of peripheral dopamine receptors by a selective DA1 antagonist, SCH 23390. 614 34

Until recently, the key pharmacologic tools necessary for major advances in understanding and studying cardiovascular and renal dopamine receptors have been lacking. This communication describes new advances in the pharmacology of dopamine receptors as studied with a series of newly synthetized benzazepines. Fenoldopam (SK&F 82526) is a selective (DA1) dopamine-receptor agonist. Initial studies with fenoldopam on splenic arterial ring segments of the rabbit have suggested that the endothelium as well as vascular smooth muscle may possess hemodynamically important dopamine receptors, and that cyclic adenosine monophosphate can be a second messenger mediating dopaminomimetic vasodilatation. Significant advances in DA1-selective antagonists have also recently been made. SK&F 83566 is a potent antagonist of both dopamine and fenoldopam in the vasculature. Dopamine-receptor selective agonists and antagonists represent an emerging strategy for the treatment of several cardiovascular diseases, including hypertension and edema. Moreover, these compounds are important tools for the characterization and study of dopamine receptors.
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PMID:Cardiovascular dopamine receptors: recent advances in agonists and antagonists of the DA1-receptor. 621 Apr 23

Dopamine has been used for many years to treat patients with severe heart failure. It is not clear whether improvements of cardiac function may be due to a direct action on heart. This study was aimed to investigate the direct action of dopamine on failing heart. we chose male Wistar rats which had undergone uninephrectomy under ether anaesthesia to induce hypertension to result in heart failure. After 5 weeks the hearts were excised and perfused according to Langerdoff's technique. Heart rate, systolic and diastolic ventricular pressures, the derivative of the intraventricular pressure time ratio, and coronary flow were measured at baseline, at 2 and 5 min and then every 5 min during a 30-min period. Rat hearts were divided into 4 groups of 5 hearts: group 1, perfused without drug; group 2, perfused with dopamine at 4 micrograms/kg/min; group 3, perfused with dopamine at 8 micrograms/kg/min; group 4, perfused with dopamine at 8 micrograms/kg/min and with 100 nM I.C.I. 118.551 (beta 2-ant: beta-2 receptors antagonist) at the same time. Our results show that dopamine induced a negative inotropic effect and a reduction of coronary flow. Moreover, there was a significant chronotropic action even when dopamine was administered at high concentrations. So we found no positive dopamine effect on isolated failured hearts of rat. This might be explained by both alpha-1-induced vasoconstriction and the stimulation of alpha-1B receptors. We conclude that the favourable effects of dopamine in heart failure could be due to DA1 vasodilation rather than to a direct inotropic action on the heart.
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PMID:Effects of dopamine on isolated failing rat heart. 755 68

To elucidate the role of the kidney dopamine system on blood pressure regulation, we investigated the developmental change of kidney dopamine receptors in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The autoradiogram of [3H]-SCH23390, a specific DA1 receptor antagonist, showed that DA1 receptors were localized mainly in the rat renal cortex. The radiolabeled receptor assay (RRA) of [3H]-spiperone was performed on 3-, 7-, and 18-week-old SHR using the homogenate of renal cortex. Neither dissociation constant (Kd) nor maximum binding capacity (Bmax) were different between SHR and WKY rats at the age of 3 and 7 weeks. Nevertheless, Kd and Bmax were significantly low in 18-week-old SHR. The systolic blood pressure of 7-, and 18-week-old SHR was significantly higher than that of age matched WKY rats. The urinary dopamine excretion in 16-week-old SHR was significantly higher than that in age-matched WKY rats, although urine volume and urinary sodium excretion were the same as those in the control in both sodium-loaded and -restricted state. In summary, although renal dopamine production was enhanced in SHR in the hypertensive state, dopamine was found not to contribute to natriuresis since the number of dopamine receptors was reduced in these rats. We also found that enhanced dopamine production in response to a salt load was lacking in these rats. These two pathological phenomena noted in the renal dopamine system play a role in the progression of hypertension in SHR.
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PMID:Developmental change of kidney dopamine receptors in spontaneously hypertensive rats. 762 Aug 26

A defective dopamine DA1 receptor has been suggested to be involved in the salt-sensitive hypertension in Dahl-S rats (DS). To investigate the consequences of this defect, the influence of DA1 receptor blockade (SCH23390) and of dopamine-synthesis inhibition (benserazide) on volume expansion (VE)-induced sodium and dopamine excretion was studied in anesthetized prehypertensive DS and salt-resistant Dahl rats (DR). Under control conditions all measured variables were equal in DR and DS. During VE (5% of BW), sodium and dopamine excretion increased similarly in the two strains. During peak natriuresis mean arterial blood pressure was 119 +/- 3 and 122 +/- 3 mm Hg, respectively. In DR treated with SCH23390, sodium excretion was only 72% of that in vehicle-treated DR. Dopamine excretion increased, however, as in vehicle-treated DR. In DS, treatment with SCH23390 did not attenuate natriuresis and dopamine excretion also increased as in vehicle-treated DS. In benserazide-pretreated DR and DS, sodium excretion during VE was similar, but only 50-51% of that in the respective vehicle-treated group. Dopamine excretion decreased by about 80% in both strains. In conclusion, prehypertensive DR and DS have a similar capacity to acutely excrete an intravenous saline load and to generate dopamine. The total dopamine involvement in VE-induced natriuresis is also comparable in the two strains, but the natriuresis mediated by DA1 receptors is pronounced in DR and non-existent in DS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo evidence for a defect in the dopamine DA1 receptor in the prehypertensive Dahl salt-sensitive rat. 771 39

Fenoldopam, a newly developed intravenous dopaminergic DA1 receptor agonist, was used in an open, prospective study for blood pressure control in 12 patients presenting with hypertensive crisis. At a dose of 0.2-0.5 microgram kg-1 min-1 fenoldopam decreased systolic blood pressure from 209 +/- 13 to 151 +/- 17 mmHg and diastolic blood pressure from 114 +/- 10 to 78 +/- 10 mmHg. Blood pressure was controlled in all 12 patients within 5-50 min. In none of the patients did rebound hypertension occur upon termination of the study medication, nor was any adverse event reported. Major hemodynamic changes induced by fenoldopam were a decrease in total peripheral resistance from 1853 +/- 611 to 1193 +/- 368 and in pulmonary vascular resistance from 252 +/- 170 to 180 +/- 74 dyne s-1 cm-5. In patients with high left ventricular filling pressure at study pulmonary capillary wedge pressure decreased while the stroke volume index and mixed venous oxygen saturation increased under fenoldopam. Thus, fenoldopam appears to be a rapid-acting, well-tolerated, and highly effective intravenous substance for the treatment of severe hypertension.
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PMID:Hemodynamic profile of intravenous fenoldopam in patients with hypertensive crisis. 790


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