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PubMed1989

[Primary orthostatic hypotension syndromes without somatic neurologic signs--idiopathic orthostatic hypotension and primary sympathicotonic orthostatic hypotension].

Idiopathic orthostatic hypotension (IOH) and primary sympathicotonic orthostatic hypotension (PSOH) are conspicuous orthostatic hypotension syndromes without overt somatic neurologic signs. IOH, also referred as pure autonomic failure, is a syndrome of chronic pandysautonomia, and its clinical features include supine hypertension, anhidrosis, impotence, neurogenic urinary and bowel disturbances. PSOH is different from IOH in which it is not accompanied with autonomic features outside of cardiovascular symptoms, and has been most commonly described in German-Scandinavian literatures. The controversy in the nosology of IOH and PSOH has prevented the both concepts from world-wide acceptance, and little has been known about IOH in Japanese population. In the present study, statistical analyses were made to elicit the cases of orthostatic hypotension syndrome without somatic neurologic signs from the pooled results of hemodynamic autonomic functional tests in our laboratory. The subjects were 287 Japanese cases comprising 253 normotensive volunteers and 34 hypertensive patients. Apart from hypertension, none of the subjects exhibited abnormal findings on physical, neurological and routine laboratory examinations. The test of 70 degrees passive head-up tilt and other hemodynamic tests were performed upon the subjects, and the results were pooled by ages. By means of the method of maximum normed residual, statistically screened out were 7 cases with extremely great orthostatic fall in systolic blood pressure (OH-I). Another OH group (OH-II) consisted of 24 cases who showed orthostatic decrease in systolic blood pressure of 30 mmHg or more, but did no fall into the extreme observation. Assuming that the orthostatic regulation mechanism of blood pressure was well maintained in the remaining 256 cases, they were used as the control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Techniques for preventing hypotension during spinal anaesthesia for caesarean section.

BACKGROUND: Maternal hypotension is the most frequent complication of a spinal anaesthetic for caesarean section with an incidence approaching 100%. Most workers define hypotension as a maternal systolic blood pressure below 70-80% of baseline recordings and/or an absolute value of < 90 -100mmHg. The frequent occurrence and rapid onset of hypotension during spinal anaesthesia has encouraged anaesthetists to try and prevent or minimise the associated maternal symptoms of nausea and vomiting during the establishment of the block. Untreated, severe hypotension can also pose serious risks to both mother (unconsciousness, pulmonary aspiration, apnoea or even cardiac arrest) and baby (impaired placental perfusion leading to hypoxia, fetal acidosis and neurological injury). A range of strategies is currently used to prevent or minimise hypotension but there is no established ideal technique. OBJECTIVES: To assess the relative efficacy and side effects of prophylactic interventions for hypotension following spinal anaesthesia for caesarean section. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register, other databases and bibliographies of relevant papers are searched according to the strategy developed for the Pregnancy and Childbirth Group as a whole. Date of last search: May 2001. SELECTION CRITERIA: All published or unpublished randomised controlled trials that compare use of an intervention to prevent hypotension with placebo or alternative treatment in patients having spinal anaesthesia for caesarean section. DATA COLLECTION AND ANALYSIS: Trials identified from searching are assessed for inclusion by the same two reviewers independently. Studies are excluded from review for the following reasons: hypotension is not an outcome measure or clearly defined prior to administering a rescue treatment; randomisation is unsatisfactory; the spinal anaesthetic technique or dose of local anaesthetic is not controlled-for; and the intervention is implemented in response to a fall in blood pressure rather than for prevention. Statistical analyses use the Review Manager software for calculation of the treatment effect as represented by the relative risks and proportional and absolute risk reductions. MAIN RESULTS: Twenty trials meet the criteria for inclusion. Four of the twelve interventions reviewed are shown to reduce the incidence of hypotension under spinal anaesthesia for caesarean section: (1) crystalloid 20ml/kg vs control, Relative Risk (RR) 0.78 (95% confidence interval (CI) 0.6, 1.0); (2) pre-emptive colloid administration vs crystalloid, (RR) 0.54 (95% CI 0.37, 0.78); (3) ephedrine vs control, RR 0.70 (95% CI 0.57, 0.85); and (4) lower limb compression vs control, RR 0.75 (95% CI 0.59, 0.94). There are no significant differences in maternal or neonatal side effects in any of the comparisons studied. REVIEWER'S CONCLUSIONS: No studied intervention has been shown to eliminate the need to treat maternal hypotension during spinal anaesthesia for caesarean section. We are unable to draw any conclusions regarding adverse effects of the studied interventions, due to their probable low incidence and the small number of women studied. Further randomised controlled trials are recommended, in particular assessing a combination of the beneficial interventions, i.e. colloid or crystalloid preloading, parenteral ephedrine administration and leg compression with bandages, stockings or inflatable boots.

Anesthesia, Obstetrical↗
PubMed2000

Dopamine versus dobutamine for hypotensive preterm infants.

BACKGROUND: Inotropes are widely used in preterm infants to treat systemic hypotension. The most commonly used drugs are dopamine and dobutamine. These agents have different modes of action which may result in different haemodynamic effects. OBJECTIVES: To compare the effectiveness and safety of dopamine and dobutamine in the treatment of systemic hypotension in preterm infants. SEARCH STRATEGY: The standard search method of the Cochrane Neonatal Review Group was used. Searches of electronic and other databases were performed. Previous reviews were searched for references to relevant trials and leading authors in the field were contacted for information about other published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials where short and/or long term effects of treatment with dopamine and dobutamine for the treatment of systemic arterial hypotension were compared were selected for this review. Trials studying newborn infants born before 37 completed weeks gestation and less than 28 days of age were eligible for inclusion. Systemic arterial hypotension was not defined specifically, but accepted as defined in individual studies. Studies were not limited by birthweight, lower gestational age threshold or by route or duration of administration of inotropic agents. Study quality and eligibility were assessed independently by each reviewer. DATA COLLECTION AND ANALYSIS: The standard method of the Cochrane Collaboration described in the Cochrane Collaboration Handbook was used to perform this systematic review. Data extraction was performed independently by each reviewer, with differences being resolved by discussion. The following outcomes were determined: mortality in the neonatal period, long term neurodevelopmental outcome, radiological evidence of severe neurological injury, short term haemodynamic changes and incidence of adverse effects. The effect of interventions is expressed either as Relative Risk (RR), Risk Difference (RD) or as Weighted Mean Difference (WMD) with their 95% Confidence Interval (CI). MAIN RESULTS: Four trials met the pre-defined criteria for inclusion in this review. There was no evidence of a significant difference between dopamine and dobutamine in terms of neonatal mortality (RD 0.02 95% CI -0.12 to 0.16), incidence of periventricular leukomalacia (RD -0.08, 95% CI -0.19 to 0.04), or severe periventricular haemorrhage (RD -0.02, 95% CI -0.13 to 0.09). Dopamine was more successful than dobutamine in treating systemic hypotension, with fewer infants having treatment failure (RD -0.29, 95% CI -0.42 to -0.17; NNT = 3.5, 95% CI 2.4 to 5.9). There was no evidence of a significant difference in change in left ventricular output when dopamine was compared with dobutamine (WMD -83 ml/kg/min, 95% CI -174 to 8 ml/kg/min). There was no evidence of a significant difference between the two agents with respect to the incidence of tachycardia (RD -0.06, 95% CI -0.25 to 0.14). None of the studies reported the incidence of adverse long term neurodevelopmental outcome. REVIEWER'S CONCLUSIONS: Dopamine is more effective than dobutamine in the short term treatment of systemic hypotension in preterm infants. There was no evidence of an effect on the incidence of adverse neuroradiological sequelae (severe periventricular haemorrhage and/or periventricular leucomalacia), or on the incidence of tachycardia. However, in the absence of data confirming long term benefit and safety of dopamine compared to dobutamine, no firm recommendations can be made regarding the choice of drug to treat hypotension.

Cardiotonic Agents↗
PubMed1999

Differential recruitment of hypothalamic neuroendocrine and ventrolateral medulla catecholamine cells by non-hypotensive and hypotensive hemorrhages.

We performed c-fos expression experiments in conscious rats to quantify the threshold and extent of activation of hypothalamic neuroendocrine cells in response to non-hypotensive and hypotensive hemorrhages allowing us to assess whether their pattern of recruitment corresponded to known oxytocin, vasopressin and ACTH release patterns. Also, because previous studies have implicated ventrolateral medulla catecholamine cells in the generation of certain hypothalamic neuroendocrine cell responses, we examined the response of ventrolateral medulla catecholamine cells to non-hypotensive and hypotensive hemorrhages and directly tested their role in regulating neuroendocrine cell responses to hypotensive hemorrhage. Animals were subjected to hemorrhages of 0, 4, 8, 12 or 16 ml/kg BW, the latter two levels being hypotensive. We found that only supraoptic nucleus vasopressin cells were significantly activated by the smallest non-hypotensive hemorrhage (4 ml/kg), which corresponds to reports that only vasopressin is released into the plasma after a small hemorrhage. Hypotensive hemorrhages resulted in significant recruitment of paraventricular and supraoptic oxytocin and vasopressin cells and parvocellular cells of the medial division of the paraventricular nucleus. Vasopressin cells were recruited in much greater numbers than oxytocin cells, which is in agreement with previous findings that there is a greater release of vasopressin than oxytocin into the plasma after hypotensive hemorrhage. In addition, medial parvocellular cells of the paraventricular nucleus, most likely to be tuberoinfundibular-projecting corticotropin-releasing factor cells, were activated by hypotensive hemorrhage only when arterial pressure dropped below 60 mmHg which also corresponds well with the plasma release response of ACTH. Ventrolateral medulla catecholamine cells were only recruited by hypotensive hemorrhages. While caution must be exercised in interpreting an absence of response, this certainly suggests that catecholamine cells are unlikely to have a role in the activation of supraoptic neurosecretory cells in response to non-hypotensive hemorrhages. Unilateral lesions of the ventrolateral medulla catecholamine cell column, corresponding primarily to the location of A1 noradrenergic cells, significantly reduced the hypotensive hemorrhage-induced activation of hypothalamic vasopressin, oxytocin and medial parvocellular paraventricular nucleus cells. This suggests that A1 noradrenergic cells contribute to the activation of these neuroendocrine cell populations, including oxytocin cells, which is an unexpected finding. More significantly, however, because the reduction in responsiveness after A1 lesions was similar for all cell categories, it seems likely that other factors must determine the differential recruitment of hypothalamic neuroendocrine cells in response to a hypotensive hemorrhage.

Animals↗
PubMed1988

The stress response to induced hypotension for cerebral aneurysm surgery: a comparison of two hypotensive techniques.

Plasma epinephrine (PE), plasma norepinephrine (PNE), plasma renin activity (PRA), mean arterial pressure (MAP) and heart rate (HR) were measured before, during and after induced hypotension in two groups of patients undergoing cerebral aneurysm surgery. In Group I isoflurane was used to maintain anaesthesia and induce hypotension. Mean PE fell significantly during hypotension and remained reduced after hypotension, mean PNE remained unchanged, while mean PRA rose slightly but not significantly during hypotension, falling again after hypotension. In Group II halothane was used to maintain anaesthesia and sodium nitroprusside to induce hypotension. During anaesthesia and surgical stimulation PNE and PRA were significantly greater compared to Group I. Mean PE, PNE and PRA all rose during hypotension and remained elevated after hypotension. The rise in PNE and PRA was statistically significant. After hypotension the MAP in Group II was significantly higher when compared to Group I. There was no significant change in HR during the study in either group. In conclusion, isoflurane-induced hypotension with isoflurane anaesthesia unlike sodium nitroprusside-induced hypotension with halothane anaesthesia attenuated the stress response.

Adult↗
PubMed1990

Influence of hypotension and hypotensive technique on the area of profound reduction in cerebral blood flow during focal cerebral ischaemia in the rat.

We have studied the effect of induced hypotension on reduction in regional cerebral blood flow (CBF) during middle cerebral artery occlusion (MCAO). Rats were anaesthetized with 2% isoflurane. MCAO was performed during four conditions: normotension (mean arterial pressure (MAP) 107 (SD 15) mm Hg); hypovolaemic hypotension (blood withdrawn to reduce MAP to 43 (2) mm Hg); nitroprusside (SNP) hypotension (MAP reduced to 45 (3) mm Hg); isoflurane hypotension (MAP reduced to 44 (3) mm Hg with 3.5 (0.48)% isoflurane). Hypotension was established before MCAO and was maintained for 10 min, at which time the dimension of the brain areas with zero CBF was determined autoradiographically. All hypotensive regimens were associated with significantly larger areas of extreme CBF reduction. In a coronal section at the centre of the MCA distribution, the area with zero CBF (expressed as a percentage of the area of the entire coronal section) was: normotension 4.7 (4.5)%; hypovolaemic hypotension 10.1 (2.8)%; nitroprusside hypotension 13.5 (2.0)%; and isoflurane hypotension 11.8 (3.9)%. There were no differences between the three hypotensive regimens. The data indicate that, when focal cerebral ischaemia occurs during hypotension (MAP 45 mm Hg) induced by any of the three regimens evaluated, extreme CBF reduction occurs over larger areas than are observed during normotension. These data confirm the importance of arterial pressure as a determinant of collateral flow during focal cerebral ischaemia.

Animals↗
PubMed1999

Hypotension in patients with coronary disease: can profound hypotensive events cause myocardial ischaemic events?

OBJECTIVE: To determine whether anginal episodes might be related to extremes of hypotension in patients with ischaemic heart disease taking drugs to treat angina and heart failure. DESIGN AND SETTING: Observational study of patients with ischaemic heart disease attending an urban tertiary referral cardiology centre. INTERVENTIONS AND OUTCOME MEASURES: A selected patient population was enrolled, having: angina on one or more hypotensive cardiovascular medications; hypotension on clinic or ambulatory measurement; and a resting ECG suitable for ambulatory monitoring. Patients had echocardiography, ambulatory blood pressure monitoring, and Holter monitoring. Hypotension induced ischaemic (HII) events were defined as episodes of ST segment ischaemia occurring at least one minute after an ambulatory blood pressure measurement (systolic/diastolic) below 100/65 mm Hg during the day, or 90/50 mm Hg at night. RESULTS: 25 suitable patients were enrolled, and 107 hypotensive events were documented. 40 ST events occurred in 14 patients, of which a quarter were symptomatic. Fourteen HII events occurred in eight patients, with 13 of the 14 preceded by a fall in diastolic pressure (median diastolic pressure 57.5 mm Hg, interquartile range 11, maximum 72 mm Hg, minimum 45 mm Hg), and six preceded by a fall in systolic pressure (chi(2) = 11.9, p < 0.001). ST events were significantly associated with preceding hypotensive events (chi(2) = 40.2, p < 0.0001). Patients with HII events were more frequently taking multiple hypotensive drug regimens (8/8 v 9/17, chi(2) = 5.54, p = 0.022). CONCLUSIONS: In patients with ischaemic heart disease and hypotension, symptomatic and silent ischaemia occurred in a temporally causal relation with hypotension, particularly for diastolic pressures, suggesting that patients with coronary disease may be susceptible to ischaemic events incurred as a result of low blood pressure caused by excessive hypotensive drug treatment.

Adrenergic beta-Antagonists↗
PubMed1986

Hypotension in end-stage renal disease: effect of postural change, exercise and angiotensin II infusion on blood pressure and plasma concentrations of angiotensin II, aldosterone and arginine vasopressin in hypotensive patients with chronic renal failure treated by dialysis.

In 16 dialysis patients, 8 hypotensive and 8 normotensive, and 8 control subjects, blood volumes were studied and angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) were measured in the supine position, after standing upright for 5 min and after a standard exercise test. In 8 hypotensive and 7 normotensive dialysis patients and in 7 control subjects, the pressor response to AII infusion was determined. Baseline values for AII, Aldo and AVP were the same in the different groups but with a much wider range in uremic patients. After standing for 5 min. both hypotensive and normotensive dialysis patients were able to maintain blood pressure without a significantly greater increase in heart rate than was seen in controls. Contrary to controls, however, all non-nephrectomized dialysis patients responded with an increase in AII and Aldo after standing for 5 min. In controls, exercise induced a clearcut increase in AII, Aldo and AVP, while no such changes were detectable in either hypotensive or normotensive dialysis patients. No significant differences in blood volumes were detectable between the groups. The pressor response to AII infusion was decreased in both normotensive and hypotensive dialysis patients compared with controls. It can be concluded that circulatory adjustment is abnormal in both hypotensive and normotensive dialysis patients as indicated by extremely high baseline levels of AII in some patients, abnormal response of the renin-angiotensin-aldosterone system and AVP to postural change and exercise and a decreased pressor response to AII infusion. However, neither these abnormalities nor changes in blood volumes can directly account for the chronic hypotension seen in some dialysis patients.

Adult↗
PubMed1989

Circulatory changes in muscle and skin arteries in orthostatic hypotension and constitutional hypotension.

It is not known whether there are vascular changes in the peripheral circulation of patients with orthostatic hypotension and patients with constitutional hypotension. Therefore, blood flow was studied simultaneously at the calf (mainly muscle circulation) and at the finger (mainly finger circulation) with ECG-triggered venous occlusion plethysmography. Calf and finger blood flow were measured for 20 min at rest and during reactive hyperaemia due to an arterial occlusion for 3 min. Vascular resistance was calculated from the blood flow and arterial blood pressure. In orthostatic hypotension there is a decreased vasodilator capacity of the calf resistance vessels and not of the finger resistance vessels. In constitutional hypotension there is a decreased vasodilator capacity of the calf and finger resistance vessels. These results suggest that there are structural or functional changes, or both, in the muscle and skin circulation of patients with constitutional hypotension, whereas there are only structural or functional changes, or both, in the muscle circulation of patients with orthostatic hypotension.

Adult↗
PubMed1986

Insulin-induced hypotension and neurogenic orthostatic hypotension.

Insulin-induced hypoglycemia induced a fall in blood pressure (BP) in patients with idiopathic orthostatic hypotension (IOH) and multiple system atrophy (MSA), but not in control subjects. Only in IOH was there a correlation between plasma norepinephrine (NE) levels and maintenance of BP during the test. The hypotension was not affected by pretreatment with propranolol. Hypotension during insulin-induced hypoglycemia is manifested in patients who lack an adequate NE response. The hypotension, however, may be due to a central action of insulin because not all MSA patients with impaired NE release become hypotensive.

Aged↗
PubMed1990

Eicosanoids as a new class of ocular hypotensive agents. 3. Prostaglandin A2-1-isopropyl ester is the most potent reported hypotensive agent on feline eyes.

It has been shown that prostaglandin A2 (PGA2) is a more potent ocular hypotensive agent in cats than other PG free acids. We report here that significant IOP reduction can be achieved in normotensive cat eyes with the use of even lower doses of PGA2-1-isopropyl ester (PGA2-IE) than with PGA2, PGF2 alpha-1-isopropyl ester (PGF2 alpha-IE), or any other known ocular hypotensive agent. Furthermore, single applications of 0.5 microgram of PGA2-IE maintain significant IOP reductions for at least 24 hr. This hypotensive effect is enhanced during the first 3-5 days of daily treatment. Significant IOP reductions were maintained for several months as long as PGA2-IE was applied daily or at least once every 48 hr. None of the cats manifested signs of discomfort in response to treatment with doses ranging from 0.10 to 1.25 micrograms of PGA2-IE. Moreover, the extent of anterior chamber flare was less than that typically observed after the topical application of hypotensive doses of PGE2, PGD2, PGF2 alpha, or the esters or tromethamine salt of PGF2 alpha. Although it is possible that the human eye would respond differently to PGs of the A type, the results of these studies suggests that PGA2-IE or other esters of derived PGs of the A type, and probably the B type, may offer significant therapeutic advantages over the PGF2 alpha tromethamine salt and PGF2 alpha-IE, which have been shown to exert significant hypotensive effects on normal and glaucomatous human eyes.

Administration, Topical↗
PubMed1986

Hypotensive response of spontaneously hypertensive rats to centrally administered diltiazem and its metabolites: in relevance to the hypotensive action by oral administration.

In order to study whether a part of the antihypertensive action of orally administered diltiazem is mediated by the central nervous system and whether metabolites of diltiazem contribute to the actions of diltiazem, we compared the effects of diltiazem and its main metabolites on blood pressure by intravenous administration with those by intracerebroventricular administration to spontaneously hypertensive rats (SHR). Contents of diltiazem and its metabolites in the brain of SHR after oral administration were also studied. Hypotensive action of intravenously administered diltiazem was stronger than that of its main metabolites in terms of potency and durability. Diltiazem (30 micrograms or more) and its main metabolites (100 micrograms) showed weak hypotensive action by intracerebroventricular administration. Oral administration of diltiazem (30 mg/kg) decreased mean blood pressure by about 40 mmHg 30 min after the administration. At this time, contents of unchanged form and metabolites of diltiazem in the brain were 0.78 +/- 0.10 and 7.58 +/- 0.89 micrograms/whole brain, respectively. It was suggested that hypotensive action of diltiazem was mainly attributable to the unchanged form and that the contribution of central action to the acute hypotensive action of diltiazem was unlikely, although centrally administered diltiazem can cause systemic hypotension.

Administration, Oral↗
PubMed1999

Cardiac evaluation in hypotension-prone and hypotension-resistant hemodialysis patients.

BACKGROUND: Hypotension during hemodialysis occurs frequently, but the precise mechanism remains unclear. In this study, the presence of myocardial ischemia and myocardial contractile reserve during infusions of the beta-adrenergic receptor agonist dobutamine was assessed by means of dobutamine-atropine stress echocardiography (DSE) in hypotension-prone (HP) and hypotension-resistant (HR) hemodialysis patients. METHODS: Eighteen HP patients (age 53 +/- 6 years) were compared with 18 HR patients (age 53 +/- 3 years), matched with respect to the duration of hemodialysis and cardiovascular history. New wall abnormalities during dobutamine stress reflect the presence of myocardial ischemia, whereas the increase in stroke index and cardiac index reflects myocardial contractile reserve. RESULTS: Wall motion score at rest (1.42 +/- 0.53 vs. 1.44 +/- 0.57) and dobutamine-induced new wall motion abnormalities (4 vs. 3 patients) between HP and HR patients were similar, but responses of cardiac index, stroke index, and systolic blood pressure to do butamine between the two groups were different. Not withstanding a similar cardiac index at rest (2.4 +/- 1.1 liter/min/m2 in HP and 2.8 +/- 1.2 liter/min/m2 in HR patients), dobutamine-induced increments in the cardiac index were considerably smaller in the former (0.8 +/- 1.3 liter/min/m2) than in the latter patients (2.3 +/- 1.6 liter/min/m2, P = 0.002), predominantly because of a progressive decrease in the stroke index in the HP patients. CONCLUSION: Impaired myocardial contractile reserve rather than ischemia is predominant in HP patients. This impaired myocardial contractile reserve may play a role in the development of hemodialysis-induced hypotension.

Adult↗
PubMed1989

Midodrine. A review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders.

Midodrine, a peripheral alpha-adrenergic agonist, finds use in the clinical management of patients with orthostatic hypotension or hypotension secondary to other clinical conditions or drug therapies. Midodrine is almost completely absorbed after oral administration and undergoes enzymatic hydrolysis to form its pharmacologically active metabolite, de-glymidodrine. In patients with refractory orthostatic hypotension oral midodrine increases standing blood pressure and improves symptoms of orthostatism, such as weakness, syncope, blurred vision and fatigue, without any associated cardiac stimulation. Comparative studies have shown midodrine to be clinically at least as effective as other sympathomimetic agents (norfenefrine, etilefrine, dimetofrine and ephedrine) and dihydroergotamine in this regard. Additionally, midodrine appears to cause less frequent and severe adverse effects associated with alpha-receptor agonism such as piloerection and urinary hesitancy. The most commonly experienced adverse effects--piloerector reactions, gastrointestinal disorders, and cardiovascular complaints--are generally mild and can be controlled by reducing the dosage of midodrine. Thus, midodrine is at least as useful as other currently available options in the management of orthostatic or secondary hypotension, and represents a stepping stone towards optimal therapy.

Animals↗
PubMed1998

Effects of hypotensive and non-hypotensive doses of manidipine on structure, responses to endothelin-1 and ICAM-1 production in mesenteric small resistance arteries of spontaneously hypertensive rats.

OBJECTIVE: We have evaluated the effects of a new calcium channel blocker, manidipine, given at both high, hypotensive and low, non-hypotensive doses, on vascular morphology, response to endothelin-1 and ICAM-1 production in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). METHODS: Ten SHR were treated with manidipine 3 mg/kg per day (high dose) and 10 with manidipine 0.3 mg/kg/per day (low dose). The drug was administered by gavage from the 4th to 12th weeks of age. Eighteen Wistar-Kyoto (WKY) rats and 18 SHR were kept untreated as controls. Rats were killed at 13 weeks. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of indexes of vascular structure (media thickness, wall thickness, media/lumen ratio). RESULTS: Systolic blood pressure was significantly reduced by the high dose of the drug, while no effect was observed with low-dose manidipine. A reduction in the media/lumen ratio was observed only in SHR treated with high-dose manidipine. The response to endothelin-1 in untreated SHR was significantly lower in comparison with WKY; a significant reduction was observed in SHR treated with high-dose manidipine. ICAM-1 vascular concentrations were higher in untreated SHR than in WKY controls. Both high- and low-dose manidipine reduced ICAM-1 concentrations toward normalization. CONCLUSIONS: Manidipine at high, hypotensive, but not at low, non-hypotensive doses has been proven to reduce structural alterations in mesenteric small resistance arteries, and to normalize vascular responses to endothelin-1. In addition, manidipine, at both low and high doses, may reduce ICAM-1 vascular production, thus suggesting a possible anti-atherogenic effect.

Animals↗
PubMed2000

Midodrine: a selective alpha-adrenergic agonist for orthostatic hypotension and dialysis hypotension.

Midodrine is an oral agent which acts as a selective peripherally-acting alpha-receptor agonist. Midodrine is a prodrug that is almost completely absorbed after oral administration and converted into its active drug de-glymidodrine in the systematic circulation, with a bioavailability of 93%. It has been used successfully in the treatment of neurogenic orthostatic hypotension and more recently, in the treatment of dialysis hypotension. It acts through vasoconstriction of the arterioles and the venous capacitance vessels, thereby increasing peripheral vascular resistance and augmenting venous return, respectively. It is a unique agent in the armamentarium against orthostatic hypotension since it has minimal cardiac and CNS effects. This article will review the literature on midodrine for conditions of autonomic dysfunction, with focus on recent studies on its use in haemodialysis patients.

Adrenergic alpha-Agonists↗
PubMed1996

[Orthostatic hypotension and postprandial hypotension].

Both orthostatic hypotension (OH) and postprandial hypotension (PPH) may result from lesions in any part of the baroreflex arc, which comprises central autonomic network, afferent pathways, efferent pathways, and neuro-vascular junction. Nonetheless, most attention has been centered to the efferent pathways to date. In the present report, I discussed on the contribution of neuro-vascular junction and central autonomic network to the development of OH and PPH. I also referred to the essential difference in pathophysiology between OH and PPH. (1) Difference between OH and PPH: Essential difference is in triggers inducing the initial blood pressure fall. The trigger in OH is gravity, while that in PPH is abnormal release of vasodilative gastroenteric peptides; the former is equally delivered to all persons living on earth, but the latter varies from person to person. (2) Neuro-vascular junction: Previous studies, in which catecholamine drip infusion tests were carried out on patients with OH, suggested that all of cardiovascular alpha-, beta 1, and beta 2 adrenoceptors gain denervation supersensitivity in OH. This view does, however, underestimate the blood pressure buffering effect of baroreflex. Because long-standing alteration in blood pressure by drip infusion of catecholamine necessarily provokes baroreflex, it is reasonable that augmented cardiovascular responses in OH are largely due to baroreflex failure. We performed bolus infusion tests of noradrenaline and isoprenaline on patients with OH, and found that alpha-adrenoceptor-mediated rise in blood pressure was comparable to control, beta 1-mediated increase in heart rate was blunted, and beta 2-mediated fall in blood pressure was enhanced in OH. It is, therefore, likely that beta 2-mediated vasodilation exceeds alpha-mediated vasoconstriction in OH. In such condition, noradrenaline may produce a paradoxical hypotensive effect, which contributes to the development of OH or PPH. (3) Central autonomic network (CAN): Clinical symptoms due to lesions within CAN are usually not manifested when the efferent sympathetic pathways are highly impaired, as in multiple system atrophy. Some variants of OH and PPH may result from lesions within CAN, however. For example, we have experienced a case of sympathotonic OH associated with herpes simplex encephalitis, in which the efferent pathways do not seem to be involved.

Eating↗