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

This symposium reviewed the fundamental principles, pharmacology, and clinical pharmacology of central alpha-adrenergic blood pressure regulating mechanisms. Fundamental principles Arterial baro- and chemoreceptor signals reach the nucleus of the tractus solitarius (NTS) via vagal and glossopharyngeal afferents. The NTS communicates with sympathetic preganglionic neurons in the spinal cord via centers and tracts in the medulla, pons, and hypothalamus that include an alpha-adrenergic inhibitory network. Descending tracts emphasized in this symposium originate in the C-1 epinephrine cells of the medulla, B-1 and B-3 serotonin cells of the medulla, and A-5 norepinephrine cells of the pons. Transmitters involved are norepinephrine, epinephrine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). Catecholamine enzymes share protein domains in their primary structures and may be coded by linked or single genes. New methods of purifying and locating alpha- and beta-receptors have been developed. Pharmacology Methyldopa, clonidine, and clonidine-like drugs lower blood pressure by stimulating postsynaptic alpha 2-receptors in a brain stem inhibitory network, which down-regulates these receptors. Alpha 1-receptors were found to be higher in normotensive than in hypertensive rats and were increased in the latter by methyldopa administration. Alpha 2-receptors were found to differ in various tissues, which permits the development of highly selective agonists and antagonists. Although alpha-methylnorepinephrine is probably the principal metabolite of methyldopa, alpha-methylepinephrine and alpha-methyldopamine may also contribute. The site of action usually is identified as the NTS. Possible roles for the descending tracts were suggested. Clinical pharmacology Methyldopa, clonidine, guanfacine, and related drugs lower blood pressure principally by CNS mechanisms but peripheral actions may also contribute.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:In summary: satellite symposium on central alpha-adrenergic blood pressure regulating mechanisms. 615 4

The effects on blood lipids and uric acid of six different antihypertensive drugs used alone, and of five different combinations of two antihypertensive drugs, are reported here. Prazosin significantly lowered serum low density lipoprotein and very low density lipoprotein (LDL + VLDL) cholesterol and total triglycerides while maintaining high density lipoprotein (HDL) levels. Atenolol lowered LDL + VLDL cholesterol slightly. Both pindolol and hydrochlorothiazide (HCTZ) were neutral, while oxprenolol increased total triglycerides. Propranolol lowered HDL cholesterol and increased total triglycerides and uric acid. The combination of prazosin plus pindolol has a direct favorable lipid profile, while the combination of propranolol plus HCTZ lowered HDL cholesterol and increased total triglycerides. The combination of propranolol plus prazosin lowered HDL cholesterol, but to a lesser degree than propranolol alone, which suggests that prazosin was not able to completely counteract the negative effects of propranolol on HDL. Methyldopa plus HCTZ, and HCTZ plus amiloride were neutral with regard to effects on blood lipids. It is suggested that the metabolic effects of antihypertensive drugs could be of special importance in the long-term treatment of mild hypertension.
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PMID:Antihypertensive drugs and blood lipids: the Oslo study. 617 60

Trophic adrenergic influences may in part potentiate the pressure dependent development of structural cardiovascular changes in hypertension. Regression of such changes by antihypertensive treatment should therefore be most successful if adrenergic blocking drugs are used. In the present study spontaneously hypertensive rats (SHR) received either alpha-methyldopa, metoprolol, felodipine, a new vasodilating Ca2+-antagonist, or metoprolol and felodipine in combination for 10 weeks. Their left ventricles were weighed and resistance vessel design was analysed using a haemodynamic technique. Arterial pressure (MAP) was equally reduced by metoprolol and felodipine. Despite their different modes of action cardiovascular design was also equally affected. The combined regimen reduced average MAP more than either drug alone. It also caused more pronounced regression of cardiovascular structural changes. Methyldopa lowered MAP less than either metoprolol or felodipine and had only modest effects on cardiovascular design. Thus, the extent of MAP reduction, regardless of which therapeutic regimen is used to induce it, determines the extent of regression of structural cardiovascular changes during antihypertensive treatment.
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PMID:Regression of structural cardiovascular changes by antihypertensive therapy in spontaneously hypertensive rats. 624 24

Serial blood samples were obtained throughout pregnancy from 11 women with essential hypertension (EHT). Seven were treated with labetalol (Trandate) and 4 with alpha -methyl dopa (Aldomet). Nine patients were well-controlled throughout pregnancy. Their mean plasma renin concentrations (PRC) followed the profile determined in 18 normal patients studied serially. They remained in the upper normal range until the last month, when both treatment groups showed a fall in PRC. Mean plasma aldosterone (ALD) also followed a normal profile until late gestation when it too showed a sharp fall. Of the two patients who developed superimposed PIH, one, who received labetalol, developed severe hypertension at 35 weeks, requiring delivery. Although PRC increased early in this pregnancy, ALD did not, remaining low throughout. Serum potassium [K+] measurements were also very low in this patient. The second patient only became hypertensive at 40 weeks and had PRC and ALD profiles resembling those in the successfully treated EHTs. There was a strong positive correlation throughout between serum potassium and ALD measurements (p less than 0.001) but none between PRC and ALD. This latter agrees with the known lack of correlation between PRC and ALD in normal pregnancy and may suggest that changes in electrolyte balance are more important stimuli to ALD secretion during pregnancy.
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PMID:Renin and aldosterone concentrations in pregnant essential hypertensives - a prospective study. 634 44

A 33 year old man with a history of recurrent episodes of orthostatic dizziness since adolescence was noted to have a supine blood pressure of 200/120 mm Hg and a standing blood pressure of 90/60 mm Hg. Results of extensive laboratory studies for secondary hypertension were negative. Studies of the autonomic nervous system function revealed normal plasma catecholamines, cold pressor test and response to 4 minute 30% of maximal static handgrip contraction and an appropriate increase in heart rate on intravenous injection of atropine. In contrast, the heart rate response to phenylephrine and sodium nitroprusside infusion, carotid massage and graded neck suction with an airtight chamber was very abnormal, indicating marked dysfunction of the afferent limb of the arterial baroreceptor reflex system. Methyldopa decreased the supine hypertension and increased the standing blood pressure.
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PMID:Primary dysfunction of the afferent limb of the arterial baroreceptor reflex system in a patient with severe supine hypertension and orthostatic hypotension. 648 Oct 19

Chemical stimulation of brain cholinergic neurons in many species can produce hypertension. Recent studies in this laboratory have demonstrated that clonidine inhibits this central cholinergic pressor response by inhibiting the biosynthesis of brain acetylcholine. This study was designed to determine whether methyldopa, like clonidine, could inhibit brain cholinergic neurons involved in cardiovascular regulation in freely-moving spontaneously hypertensive rats (SHR). Intravenous (i.v.) injection of methyldopa (50-200 mg/kg) produced a dose-related fall in blood pressure (29/15-54/33 mm Hg) in SHR. Intracerebroventricular (i.c.v.) injection of hemicholinium-3 (HC-3) in SHR evoked a fall in arterial pressure through inhibition of acetylcholine synthesis. Doses of HC-3 (10 micrograms, or 15 micrograms, i.c.v.) and methyldopa (50 mg/kg, i.v.) were administered to produce small reductions in arterial pressure in SHR (7-14 mm Hg diastolic, respectively). When the two agents were injected simultaneously, however, a greater than additive response was obtained (p less than 0.05). Central injection of echothiophate (a long-acting cholinesterase inhibitor) to potentiate brain cholinergic activity resulted in a sustained hypertensive response (greater than 40 mm Hg) in SHR for at least 150 minutes. Simultaneous injection of or pretreatment with methyldopa (100 mg/kg, i.v.) inhibited the pressor response to echothiophate over a time course similar to its antihypertensive response in untreated SHR. Methyldopa, however, was completely ineffective in altering the hypertensive response to central injection of carbachol (1 microgram, i.c.v.). This difference in methyldopa susceptibility between the indirect-acting (echothiophate) and direct-acting (carbachol) cholinergic agonists may be related to an inhibiting effect of methyldopa on brain acetylcholine release.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Effect of methyldopa on brain cholinergic neurons involved in cardiovascular regulation. A study in conscious spontaneously hypertensive rats. 650 Jun 69

Blood pressure; extracellular fluid volume; renal plasma flow; glomerular filtration rate; plasma concentrations of renin, angiotensin, aldosterone, desoxycorticosterone, and prostaglandins; responses to infused angiotensin; and many other factors are altered during normal and hypertensive gestation. The diagnosis of the exact disease process responsible for hypertension in pregnancy in an individual patient is extremely difficult if based solely on clinical criteria. The American College of Obstetricians and Gynecologists has suggested the following clinical classifications: (1) preeclampsia-eclampsia, (2) chronic hypertension of whatever cause, (3) chronic hypertension with superimposed preeclampsia, and (4) late or transient hypertension. The three broad categories of renal disease responsible for these clinical syndromes are: (1) preeclampsia-eclampsia, (2) hypertensive changes, and (3) various primary renal diseases. Controversy abounds regarding the aggressiveness of therapy in this syndrome. We prefer a middle-of-the-road approach, bringing blood pressure down to the range of 95 to 100 mm Hg. Hydralazine and Aldomet are the usual drugs of choice. Any intervening nervous system hyperexcitability suggests impending eclampsia and should be immediately treated with magnesium sulfate. The long-term prognosis for the mother with pure preeclampsia appears to be excellent. Most infants born of hypertensive gestations are small for date, with a prognosis that is also affected by the underlying disease of the mother.
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PMID:Hypertension in pregnancy. 655 34

Our purpose was to describe changes in potassium disposition with antirenin antihypertensives during dynamic physical activity in normal subjects receiving methyldopa and propranolol. Before the study, 2 hr after dosing and coincident with immediate preexercise on treadmill (at graded increases of exercise), and 2 hr after exercise, blood was sampled for determination of potassium, renin, aldosterone, and catecholamine levels. Blood pressure and heart rate were measured. The results demonstrate no greater increase in potassium after single or multiple doses of methyldopa than after placebo. After the first dose of propranolol there was a greater rise in potassium over that with placebo, but it was not observed after multiple doses, which may be related to the low doses. There were minor, but significant, changes in norepinephrine, renin, and systolic pressure with multiple-dose methyldopa and in renin, heart rate, and systolic and diastolic pressure with propranolol. Overall, the adrenergic responses to exercise win methyldopa and propranolol were biochemically altered rather than functionally impaired. The latter is related to dose and the underlying age and state of health of our subjects. Methyldopa (or clonidine) may be useful in patients with hypertension who exercise and are predisposed to pertubations in potassium disposition.
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PMID:Biochemical and dynamic responses to single and repeated doses of methyldopa and propranolol during dynamic physical activity. 675 10

We present the case of a 28-year-old man being treated with Nardil for chronic depression who developed a hypertensive crisis and a severe occipital headache one hour after ingesting an over-the-counter appetite suppressant. The adverse reactions between MAO inhibitors and phenylpropanolamine and discussed, as are the dangers of using Demerol to treat the headache and Aldomet to treat the hypertension.
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PMID:Hypertensive crisis resulting from an MAO inhibitor and an over-the-counter appetite suppressant. 711 95

Collagen synthesis, content, and concentration were determined in the hypertrophied intima media of thoracic aortas from 10-, 15-, and 20-week-old spontaneously hypertensive rats (SHR). Although the rates of aortic collagen synthesis declined with age, the dry weight of the intima media and the total collagen content increased proportionally. Collagen concentration thus remained unchanged. Methyldopa was administered orally to SHR when they were 12 to 15 weeks of age, when their body weight were identical to the untreated group. Blood pressure and the degree of aortic medial hypertrophy, judged by medial dry weight per kilogram body weight, were significantly lower compared with untreated SHR. Collagen synthesis was likewise decreased to a mean rate not significantly higher than age-matched normotensive Wistar-Kyoto controls. This reduction in collagen synthesis, however, was not sufficient to decrease measurably the total collagen content of the aortas compared with untreated SHR. Since medial dry weights were lower in the treated rats, collagen concentration in aortas from SHR given methyldopa for 3 weeks was actually increased. The increase in collagen concentration also suggests that medial hypertrophy was reversed.
Hypertension
PMID:Collagen metabolism and reversal of aortic medial hypertrophy in spontaneously hypertensive rats treated with methyldopa. 730 9


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