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Biomedical subjects

H Gavras

Publications and source records attributed to H Gavras.

At least 127 records · Page 7Linked to original sources
PubMed1989

Bradykinin antagonism and prostaglandins in blood pressure regulation.

These experiments were designed to analyze the interaction of a bradykinin antagonist with prostaglandins in blood pressure regulation of normotensive rats. Male Wistar rats, divided into three groups, received a 5-minute intra-arterial infusion of the bradykinin antagonist [( DArgo-Hyp3-Thi5,8-DPhe7]BK-TFA) at 250 micrograms/min. Groups were either intact rats (group I, n = 5), pretreated with indomethacin (group II, n = 10), or pretreated with both indomethacin and prazosin (group III, n = 8). The bradykinin antagonist infusion, which was shown to inhibit exogenous bradykinin by greater than 76% in intact animals, did not alter mean arterial pressure in group I rats despite a twofold increase in norepinephrine and a threefold increase in epinephrine. Group II rats presented a progressive increase in mean arterial pressure during the bradykinin antagonist infusion (14 +/- 3 mm Hg), with no statistically significant change in plasma catecholamines. Group III, with lower baseline mean arterial pressure due to alpha 1-adrenergic blockade, had an increase in mean arterial pressure comparable with group II during bradykinin antagonist infusion (22 +/- 5 mm Hg), confirming that this response was not sympathetically mediated. We conclude that in normotensive rats bradykinin plays a role in blood pressure regulation that is closely linked to that of prostaglandins and that points to a balance between these systems.

Adrenergic alpha-Antagonists↗
PubMed1989

Intravenous dilevalol in the treatment of severe hypertension.

Dilevalol, the stereoisomer of labetalol, was given in repeated incremental intravenous bolus injections to 10 patients with severe hypertension requiring urgent blood pressure lowering. The mean cumulative dose of dilevalol was 445 +/- 165 mg. Blood pressure was reduced from 201 +/- 33/131 +/- 13 to 150 +/- 12/109 +/- 7 mm Hg (p less than 0.01) and heart rate did not change significantly. In only one patient was the study discontinued because of side effects (nausea and dizziness). There were no other clinically significant adverse reactions and no change was observed in electrocardiogram or routine biochemical and hematologic tests. Five of these patients, who achieved diastolic blood pressure of less than or equal to 105 mm Hg, participated in a subsequent outpatient phase of the study with combination of oral dilevalol with hydrochlorothiazide. Of these only one achieved good blood pressure control. We concluded that in such severely hypertensive patients intravenous dilevalol was safe and effective for the short-term lowering of blood pressure. However, long-term outpatient maintenance with this drug needs further evaluation.

Adult↗
PubMed1989

Dilevalol in severe hypertension. A multicenter trial of bolus intravenous dosing.

Dilevalol, the R-R optical isomer of labetalol, a nonselective beta-antagonist with vasodilation from selective beta 2 agonism, was administered in sequential multiple bolus intravenous injections of 10 to 100 mg in total doses ranging from 35 to 585 mg (mean dose, 414 mg) to 101 patients with supine diastolic blood pressures above 120 mm Hg. Mean blood pressure was reduced from 200 (+/- 3)/129 (+/- 1) mm Hg to 149 (+/- 2)/101 (+/- 1) mm Hg, a mean reduction of 51/28 mm Hg. The therapeutic goal was established as a reduction in supine diastolic blood pressure to less than 100 mm Hg or a reduction of at least 30 mm Hg. This was achieved in 62 (61%) of 101 patients, with an additional 7 patients having a final supine diastolic blood pressure of 100 mm Hg. Treatment with dilevalol was less successful in black male patients than in the group at large. There was a tendency for older patients to respond better than younger patients. Prior recent treatment of patients with beta-adrenergic antagonists decreased the effectiveness of the drug. Significant orthostatic hypotension was not noted. Sixty-four patients were transferred to oral dilevalol treatment in combination with a diuretic, and blood pressure in this group averaged 160/100 mm Hg after 1 month of therapy. Dilevalol appears to be a safe and effective drug that can be used intravenously successfully in the majority of patients with severe hypertension and provides an alternative to therapy with other agents. It also is a useful agent for oral treatment of these patients after successful intravenous therapy.

Administration, Oral↗
PubMed1988

Central sympathetic stimulation produced by saline application into the nucleus tractus solitarii area of conscious rats.

Hypertonic saline 4% was microinjected into the area of the nucleus tractus solitarii (NTS) of conscious rats. The experiments were designed to explore the systemic hormonal responses and the contribution of various hormones to the hypertensive effect elicited by this procedure. A mean blood pressure rise to 155 +/- 3 mmHg (as compared to 119 +/- 2 in rats receiving the same volume of equiosmolar dextrose solution, P less than 0.05) was accompanied by significant rises in plasma norepinephrine (0.556 +/- 0.128 ng/ml) and epinephrine (0.970 +/- 0.287 ng/ml) as compared to control rats receiving dextrose or control rats having only the cannula implanted, without microinjection. There was no significant change in plasma renin activity or plasma vasopressin levels, and the blood pressure rise could not be prevented or reversed by an angiotensin-converting enzyme inhibitor. The data are consistent with the hypothesis that the hypertensive response to this procedure is mainly due to an acute stimulation of central sympathetic neurons.

Adrenergic Fibers↗
PubMed1988

Atrial natriuretic peptide inhibits the agonist-induced increase in extent of myosin light chain phosphorylation in aortic smooth muscle.

The effect of atrial natriuretic peptide (ANP) on angiotensin II- and histamine-induced contraction and muscle light chain phosphorylation was examined in strips of rabbit aorta smooth muscle. Preincubation of strips with 10(-7) M ANP prior to addition of either agonist inhibits both the increase in extent of myosin light chain phosphorylation and the contractile response to either 5 x 10(-8) M angiotensin II or 10(-5) M histamine without inhibiting the agonist-induced increase in the intracellular free Ca2+ concentration. Furthermore, in muscle strips precontracted with either angiotensin II or histamine, addition of ANP leads to a prompt relaxation and a prompt decrease in the extent of myosin light chain phosphorylation. These data argue that ANP uncouples the initial agonist-induced Ca2+ transient from the increase in extent of myosin light chain phosphorylation either by inhibiting the Ca2+-dependent activation of myosin light chain kinase or stimulating the activity of a phosphoprotein phosphatase capable of bringing about the rapid dephosphorylation of phosphorylated myosin light chains.

Aequorin↗
PubMed1988

Acute effects of the new angiotensin-converting enzyme inhibitor cilazapril: a pilot study.

This study assesses the magnitude and duration of action of three different oral doses of the new orally active angiotensin-converting enzyme (ACE) inhibitor RO 312848 (cilazapril, Hoffman-LaRoche, Nutley, NJ) on blood pressure and plasma ACE levels. Twelve hypertensive patients were separated into two groups: Group A (n = 6) received two single daily doses of 5 and 10 mg, each preceded and followed by two placebo days, and Group B (n = 6) received 10 and 20 mg on an identical protocol. The onset and duration of an appreciable blood pressure lowering effects were at 2 hours and at least for 12 hours, respectively, whereas suppression of ACE levels occurred at 1 hour and lasted for more than 72 hours. Response of these two parameters was partial after 5 mg, but was maximal after 10 mg and did not increase further with the 20-mg dose. A 5-10 mg dose daily may be sufficient to maintain chronic blood pressure control with this agent, but long-term dose trials are necessary to establish its clinical utility.

Adult↗
PubMed1988

Renin-angiotensin and vasopressin in the development of salt-induced hypertension.

The purpose of this study was to assess the participation and interaction of the renin-angiotensin system and vasopressin in the early stages of the development of salt-induced hypertension. Subtotally nephrectomized rats, fed 1% saline, were treated over a 10-day period with either an antivasopressor V1 antagonist (by osmotic minipump) or an angiotensin converting enzyme inhibitor (either captopril or ramipril, given daily by oral gavage), or a combination of the two modes of treatment. Surprisingly, only ramipril (either alone or in combination with the V1 antagonist) could prevent the development of hypertension in these animals. Our data would not permit conclusion as to whether the different capacity of these agents to prevent salt-induced hypertension was due to a different degree of penetration into the central nervous system, or to some other property.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

The role of vasopressin in blood pressure maintenance in diabetic orthostatic hypotension.

The purpose of these studies was to assess the role of vasopressin in maintaining supine and upright blood pressures in hypertensive diabetic subjects. Patients with (n = 6) or without (n = 10) evidence of autonomic insufficiency had blood pressure and heart rate monitored before and after receiving an intravenous injection of 0.5 mg of a V1 vasopressin inhibitor. None of the patients had supine changes in blood pressure or heart rate. However, upon assuming the erect position, the six patients with preexisting orthostatic hypotension had an average blood pressure fall of 44 mm Hg after vasopressin inhibition (as opposed to 20 mm Hg before), accompanied by a modest rise in heart rate of 20 beats/min. Those without autonomic dysfunction were separated into two subgroups. Four developed an average fall in orthostatic blood pressure of 18 mm Hg after vasopressin inhibition, whereas the remaining six had no change. There were no distinguishing hormonal characteristics (vasopressin, renin, and catecholamine levels) between the groups, but in the patients with autonomic dysfunction, the renin level failed to rise when upright. We conclude that vasopressin plays an important role in preventing or minimizing orthostatic hypotension in diabetic patients. Its pressor contribution is crucial in those with autonomic insufficiency and impaired renin and sympathetic responses, in whom the pressor effectiveness of vasopressin is greatly enhanced.

Arginine Vasopressin↗
PubMed1988

Angiotensin converting enzyme inhibitors. Properties and side effects.

The purpose of this brief review is to separate the characteristic properties and side effects attributable to the pharmacology of the whole class of angiotensin converting enzyme (ACE) inhibitors from those attributable to the chemical structure and kinetics of each particular ACE inhibitor. The former would be predictable and probably similar for all agents and, therefore, would be expected to recur with each agent, whereas the latter are likely to be characteristic of individual compounds and may be avoidable by changing to another compound with similar pharmacology but different molecular structure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Vascular and sympathoadrenal responses to bradykinin and a bradykinin analogue.

These experiments were designed to assess the interaction of bradykinin and its antagonist (Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg-trifluoroacetic acid) with the sympathoadrenal system. Three groups of male Wistar rats received 5-minute intra-arterial infusions of either dextrose (Group 1, n = 6), bradykinin, 250 micrograms/min (Group 2, n = 5), or bradykinin, 25 micrograms/min (Group 3, n = 4). Six other groups received a similar infusion of the bradykinin antagonist at 250 micrograms/min. They were either intact rats (Group 4, n = 10) or rats previously submitted to chemical sympathectomy (Group 5, n = 17), to adrenal enucleation (Group 6, n = 8), to combined alpha-adrenergic and beta-adrenergic blockade (Group 7, n = 7), to alpha 1-adrenergic receptor blockade (Group 8, n = 8), or to alpha 2-adrenergic receptor blockade (Group 9, n = 8). Bradykinin infusion produced a sustained fall in mean arterial pressure (MAP) in Groups 2 and 3 (by -48 +/- 3 and -36 +/- 7 mm Hg, respectively) associated with similar increases in plasma epinephrine levels (100-fold), and norepinephrine (sevenfold) as compared with Group 1. The bradykinin antagonist infusion in intact rats produced a 23 +/- 4 mm Hg rise in MAP associated with a sixfold increase in epinephrine and a twofold increase in norepinephrine. Group 5 rats with lower baseline catecholamine levels had an even larger MAP rise (30 +/- 6 mm Hg) accompanied by a rise in epinephrine and norepinephrine proportionally similar to that of intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

Regulation of renin gene expression in hypertensive rats.

A carboxy terminal renin complementary DNA (cDNA) clone from rat kidney was isolated, characterized, and used as a probe for renin messenger RNA (mRNA) quantification in normotensive and hypertensive rats. RNA blotting analysis detected renin mRNA in control kidney and brain. Deoxycorticosterone acetate (DOCA) and high salt (1%) treatment of experimental animals resulted in a greater than 95% decrease in the content of renin mRNA in the kidney, as compared with values in control rats receiving 0.4% NaCl in their diet. In contrast, high salt (1%) treatment alone caused only a twofold decrease in kidney renin mRNA content, as compared with values in controls. DOCA and low salt (0.04%) or low salt (0.04%) treatment alone caused a 1.5-fold increase in the kidney renin mRNA content, as compared with values in control rats. These results indicate that DOCA and salt have a synergistic effect in depressing renin mRNA levels in kidney. Clipping of the left renal artery caused a threefold increase in the steady state level of renin mRNA in the ischemic kidney and a 0.5-fold decrease in the hypertrophied kidney. The data are consistent with the hypothesis that blood pressure and other stimuli regulate the expression of the renin gene in vivo.

Amino Acid Sequence↗
PubMed1987

Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system.

The results of a multicenter trial conducted in order to determine the therapeutic efficacy of the gastrointestinal therapeutic system (GITS) formulation of nifedipine in comparison with hydrochlorothiazide and placebo in the management of mild to moderate essential hypertension are presented. During a one-week wash-out phase, antihypertensive therapy was discontinued in all patients. After a three-week single-blind placebo period, eligible patients were randomly assigned in a double-blind fashion to one of three treatment groups for a one-week titration period and a nine-week efficacy period. Patients received either nifedipine GITS, 30 or 60 mg daily; hydrochlorothiazide, 25 or 50 mg daily; or placebo. Sitting and standing blood pressures decreased by an average 11.6/10.4 and 10.8/10.8 mm Hg, respectively, with nifedipine GITS therapy, and 14.8/10.8 and 14.3/8.2 mm Hg, respectively, with hydrochlorothiazide therapy. Compared with placebo, these changes were highly significant for both sitting (p less than or equal to 0.005) and standing (p less than or equal to 0.02) measurements. Heart rate remained essentially unchanged in all three groups. It was therefore concluded that monotherapy with nifedipine GITS, at doses of 30 or 60 mg given once daily, effectively reduces blood pressure in patients with hypertension to a degree comparable with that seen in hydrochlorothiazide therapy.

Adult↗
PubMed1987

Stimulation of vasopressin by calcium microinjections in the area of the paraventricular nucleus of the hypothalamus.

The present experiments were designed to investigate the effect of local calcium application on the paraventricular nucleus (PVN) on arginine-vasopressin (AVP) release and blood pressure. A microinjection of 2 microliter of calcium gluconate 10% in the PVN elevated AVP levels to 71.6 +/- 8.7 pg/ml compared to 3.3 +/- 0.6 pg/ml in control rats receiving iso-osmolar solution of dextrose 11% (P less than 0.001), whereas peripheral plasma epinephrine and norepinephrine were normal. Despite the increase of plasma AVP levels, blood pressure and heart rate remained unchanged indicating that other unknown mechanisms counteract AVP's pressor effect. These data suggest that locally applied Ca2+ in the vasopressinergic neurons of the hypothalamus strongly stimulates the release of AVP.

Animals↗
PubMed1987

Abnormal glucoregulation during exercise in type II (non-insulin-dependent) diabetes.

We studied the effects of exercise on the levels of plasma glucose and glucoregulatory hormones before and after 6 weeks of thrice-weekly physical training in 20 sedentary type II (non-insulin-dependent) diabetic patients and 11 control subjects matched for previous physical activity. Parameters were measured at rest, after 30 minutes of bicycle exercise at 70% to 75% of maximal oxygen uptake, and after 30 minutes of recovery. In the untrained state exercise resulted in a decrease in plasma glucose levels in diabetics but not in controls (-12 +/- 5 v + 4 +/- 2 mg/dL, P less than .01) and the expected drop in plasma insulin level was absent in diabetics. These differences in glucose and insulin response persisted after physical training. There was a tendency for patients with diabetes to have a smaller R-R interval variation during deep breathing, an abnormal resting heart rate response to physical training, and a lesser increment in plasma epinephrine levels following exercise, findings consistent with autonomic dysfunction. Physical training resulted in a blunting of the exercise-induced increment of plasma epinephrine, growth hormone, and lactate levels in control subjects, but not in diabetics. Our data demonstrate a hypoglycemic effect of exercise in mildly hyperglycemic nonobese type II diabetics. Possible causative factors include: hyperglycemia per se, a lack of physiologic suppression of plasma insulin, and abnormalities of autonomic or hypothalamic regulatory function.

Blood Glucose↗