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H Gavras

Publications and source records attributed to H Gavras.

At least 145 records · Page 8Linked to original sources
PubMed1987

Central catecholamines and alpha-adrenoceptors in acute hypertension induced by intracerebroventricular hypertonic saline.

We measured the tissue content of catecholamines and the numbers and affinities of alpha 1- and alpha 2-adrenergic receptors in specific areas of the hypothalamus and medulla oblongata of rats treated with intracerebroventricular microinjection of hypertonic saline, in comparison to controls treated with an equal volume of iso-osmolar dextrose solution. Rats given 20 microliter of 4% NaCl into the lateral ventricle showed an average rise in blood pressure of 14 +/- 2 mmHg and a decrease in heart rate of 63 +/- 11 beats/min (P less than 0.001 for both), associated with dopamine suppression in the anteroventral area of the third ventricle (AV3V) and increased concentrations of dopamine in the C2 region of the medulla and of epinephrine in the area postrema. Affinities of medullary alpha 2-adrenoceptors were decreased in the saline-treated rats, whereas the number of receptors tended to be higher. It is suggested that sodium may produce its pressor effect by diminishing the affinity of central alpha 2-adrenoceptors for neurotransmitters, resulting in disinhibition of certain sympathoinhibitory neurons and increased sympathetic outflow.

Animals↗
PubMed1987

Contribution of bradykinin to maintenance of normal blood pressure.

The purpose of these experiments was to investigate whether the vasodilator tissue hormone bradykinin contributes to the maintenance of normal blood pressure. A newly synthesized peptide competitive antagonist of bradykinin, the compound Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg-trifluoracetic acid (B3852), capable of inhibiting the depressor effect of exogenous bradykinin by over 50%, was infused into 10 normotensive rats at a rate of 500 micrograms/0.1 ml/min. Blood pressure rose immediately, from a baseline of 104 +/- 5 to 131 +/- 7 mm Hg at the end of a 5-minute infusion, and returned to baseline within 2 to 3 minutes after discontinuation of the infusion. When similar doses were administered by continuous infusion to previously nephrectomized rats (n = 5) or as an acute bolus to adrenalectomized rats (n = 5), blood pressure rose from 111 +/- 3 to 125 +/- 5 mm Hg and from 112 +/- 4 to 128 +/- 5 mm Hg, respectively. The data suggest that a vasodepressor action of endogenous bradykinin contributes to maintenance of normal peripheral vascular tone, and that this action is not mediated through adrenal catecholamines or renomedullary prostaglandins.

Animals↗
PubMed1987

Vasopressin in end-stage renal disease: relationship to salt, catecholamines and renin activity.

The blood pressure changes and behavior of vasoactive hormones after various stimuli were studied in eighteen patients with end-stage renal disease maintained on chronic hemodialysis. Group A patients (n = 9) were not subject to intra- or post-dialysis hypotensive episodes, and Group B (n = 9) frequently had such episodes. A 500 ml hypertonic saline infusion produced no change in blood pressure in either group, despite significant rise of vasopressin levels in both. Plasma renin activity levels were similar and became appropriately suppressed by the infusion in both groups, whereas norepinephrine rose significantly only in Group A, but not Group B where it was already higher at baseline. The regular dialysis session produced, as expected, a significantly more profound hypotensive effect in Group B, but was accompanied in both groups by decrease in vasopressin and increase in plasma renin activity. Norepinephrine change differed in the two groups: it decreased in Group A as expected from its capacity to be dialyzed, but rose in several hypotensive patients in Group B, indicating appropriate response to baroreceptor stimulation and leading to an unchanged average. These findings suggest that dialysis-induced hypotensive episodes are not necessarily associated with autonomic neuropathy or with abnormal patterns of vasopressor hormone response to stimuli. They also shed new light on the factors regulating vasopressin secretion under these circumstances, since they indicate that the osmoreceptor and/or sodium-sensitive receptor may be a more dominant mechanism in the regulation of vasopressin release than the volumetric mechanism responding to fluid volume changes.

Adult↗
PubMed1987

The antihypertensive contribution of bradykinin as assessed by a specific bradykinin antagonist.

A new specific antagonist of bradykinin was used to examine the contribution of bradykinin to the depressor effect of different antihypertensive drugs in two-kidney renovascular rats. First we tested the inhibitory capacity of this peptide for exogenously injected bradykinin (75-200 ng). An inhibition of the vasodepressor action of bradykinin by over 50% was found when the bradykinin inhibitor was infused at a rate of 40 micrograms/min, with little difference at higher rates of infusion. We then infused this inhibitor in four groups of renovascular hypertensive rats. In three groups the blood pressure had been decreased by pretreatment either with the converting enzyme inhibitor MK 421, saralasin or sodium nitroprusside, respectively. The fourth group received no pretreatment. Infusion of the inhibitor produced an immediate increase in blood pressure by 30% only in the MK 421 group, but no change in the three other groups. These results indicate that bradykinin is involved in the decrease of blood pressure produced by converting enzyme inhibition in experimental renovascular hypertension.

Animals↗
PubMed1987

Efficacy and tolerability of enalapril monotherapy in mild-to-moderate hypertension in older patients compared to younger patients.

In an eight-week, multicenter open-label study of enalapril monotherapy for mild-to-moderate essential hypertension, data for 115 of the 276 participants between the ages of 55 and 75 years (whites, n = 90; blacks, n = 25) were analyzed. These data were compared with similar data for the study subset of 92 younger patients between the ages of 21 and 45 years (whites, n = 58; blacks, n = 34). The most striking finding was the overall lack of significant differences in response between older and younger patients. There were, however, significant differences in response to therapy between the two racial groups studied. In the older group, normotension was achieved in 66% of white patients and 60% of black patients with a single daily dose of enalapril ranging from 5 to 40 mg; the group means, 13 +/- 1 mg in whites vs 22 +/- 2 mg in blacks, differed significantly (P less than 0.05). Thirty-one percent of older white patients attained normotension with a daily dosage of 5 mg, whereas only 4% of black patients in this age group did so. Only 4% of the older white patients but 24% of the older black patients reached the highest recommended daily dosage of 40 mg of enalapril. Adverse reactions occurred in 11% of the older white patients and 16% of the older black patients (a nonsignificant difference), consisting mostly of gastrointestinal discomfort, malaise, dizziness, and pruritus. There were no significant biochemical abnormalities, the only consistent change being a slight increase in mean plasma potassium from 4.34 to 4.45 mEq/L in older whites (P less than 0.05). Enalapril appeared to be generally effective and well tolerated in the management of mild-to-moderate hypertension in the older subset of patients in this study. Efficacy and tolerability data for older and younger patients were comparable.

Adult↗
PubMed1987

Double-blind, placebo-controlled trial of twice-daily nifedipine as a step-2 agent in mild essential hypertension.

Nifedipine is a calcium-channel blocker that produces vasodilatation and decreased peripheral resistance in humans. Several clinical reports document blood-pressure-lowering effects of nifedipine with either acute or chronic administration. Little data are available to evaluate sustained-release nifedipine as a step-2 agent. We performed a multicenter double-blind, placebo-controlled trial of twice-daily nifedipine in the treatment of mild essential hypertension not controlled by diuretic alone. Seventy-one subjects completed 8 weeks of treatment with nifedipine or placebo in combination with a stable dose of diuretic. Treatment groups were comparable with respect to age, sex, race, duration of hypertension, and pretreatment weight. Baseline supine blood pressure was no different in the two treatment groups (144 +/- 15/98 +/- 6 mmHg in the nifedipine/diuretic-treated group and 145 +/- 16/98 +/- 6 mmHg in the placebo/diuretic-treated group). After 8 weeks of treatment, supine blood pressure was 132 +/- 11/88 +/- 6 mmHg in the nifedipine/diuretic-treated group and 140 +/- 16/92 +/- 8 mmHg in the placebo/diuretic-treated subjects (p less than 0.01 for both systolic and diastolic blood pressure when compared to placebo/diuretic). Nifedipine with diuretic had similar effects on standing blood pressure. Nifedipine/diuretic decreased blood pressure from baseline values within 1 week of treatment, and the effect persisted for 8 weeks. Heart rate increased in nifedipine/diuretic-treated subjects during the first 2 weeks of treatment but returned to baseline by 4 weeks. No laboratory abnormalities could be attributed to nifedipine/diuretic treatment. Side effects were mild and infrequent. In summary, nifedipine/diuretic is effective and well tolerated in the treatment of uncomplicated essential hypertension inadequately controlled with diuretic therapy alone.

Adult↗
PubMed1986

Clinical utility of angiotensin converting enzyme inhibitors in hypertension.

Oral angiotensin converting enzyme inhibition was introduced eight years ago and is becoming increasingly popular for the treatment of hypertension and congestive heart failure. This treatment causes blood pressure lowering associated with suppression of angiotensin and aldosterone, lack of orthostatic hypotension or metabolic disturbances, redistribution of regional blood flows in favor of vital organs and, in the long term, decreased sympathetic drive and regression of left ventricular hypertrophy. It is effective as monotherapy in more than 50 percent of unselected patients; addition of a diuretic increases the percentage of responders to more than 80 percent. It is the treatment of choice for patients with concurrent diabetes, asthma, gout, depression, or very active life-style. Side effects, observed originally in patients with severe hypertension and renal failure treated with very high doses of captopril, are rare in otherwise healthy hypertensive patients receiving smaller doses of this drug and virtually absent with second-generation angiotensin converting enzyme inhibitors like enalapril.

Administration, Oral↗
PubMed1986

Norepinephrine applied in the paraventricular hypothalamic nucleus stimulates vasopressin release.

The present experiments were designed to investigate the effect of norepinephrine (NE) applied directly in the area of the paraventricular nucleus (PVN) of the hypothalamus on arginine-vasopressin (AVP) release and blood pressure. A microinjection of 0.4 micrograms NE in the PNV produced a plasma AVP level of 26.3 +/- 5.3 pg/ml compared to 5.3 +/- 0.6 pg/ml in controls receiving dextrose (P less than 0.001). This rise was associated with blood pressure elevations varying between 10 and 13 mm Hg, lasting for about 5 min. Systemic injection of an antivasopressor AVP antagonist reversed or prevented the blood pressure rise induced by NE microinjection. The data suggest that locally applied NE in vasopressinergic neurons of the hypothalamus stimulates the release of AVP and induces an AVP-dependent rise in blood pressure.

Animals↗
PubMed1986

Enalaprilat in hypertensive emergencies.

Enalaprilat (MK-422), an intravenously administered angiotensin-converting enzyme inhibitor, which is the parent compound of the oral angiotensin-converting enzyme inhibitor enalapril (MK-421), was studied in 11 patients with asymptomatic accelerated hypertension. Each patient received an initial intravenous dose of 1 mg, followed at one-hour intervals by enalaprilat 10 mg, furosemide 40 mg, and enalaprilat 40 mg. Six of 11 patients responded with a drop in mean arterial pressure greater than 15 mm Hg to diastolic levels below 110 mm Hg; there were four partial responders and one nonresponder. Pretreatment renins were not predictive of blood pressure response. No patient had any adverse reaction to the drug; there were no significant changes in posttreatment laboratory values. We conclude that enalaprilat is an effective, well-tolerated agent for the treatment of uncomplicated accelerated hypertension and its use does not imperil nonresponding uncomplicated patients.

Adult↗
PubMed1986

Contribution of vasopressin to vasoconstriction in patients with congestive heart failure: comparison with the renin-angiotensin system and the sympathetic nervous system.

Ten patients with advanced congestive heart failure were treated with an arginine vasopressin V1 antagonist during hemodynamic monitoring to determine the contribution of vasopressin to vasoconstriction in this disorder. The vasopressin antagonist caused a decrease in systemic vascular resistance in the three patients whose plasma vasopressin was greater than 4.0 pg/ml (average for the group was 2.4 +/- 0.6). Plasma vasopressin concentration correlated with the percent decrease of systemic vascular resistance (r = 0.70, p less than 0.025), serum sodium (r = 0.72, p less than 0.02) and serum creatinine (r = 0.85, p less than 0.005). To compare the relative roles of vasopressin, the renin-angiotensin system and the sympathetic nervous system, these patients also received captopril and phentolamine. Captopril decreased systemic vascular resistance by 20% (p less than 0.05), mostly in patients with high plasma renin activity. Levels of plasma renin activity ranged between 1 and 46 ng/ml per h (average 14.7 +/- 5.7) and correlated with serum sodium (r = 0.77, p less than 0.025), serum creatinine (r = 0.73, p less than 0.025) and right atrial pressure (r = 0.67, p less than 0.05). Phentolamine decreased systemic vascular resistance in all patients (average 34%, p less than 0.01), but the decrease did not correlate with the pretreatment norepinephrine concentration. Norepinephrine levels were elevated in all patients (694 +/- 110 pg/ml) and correlated with baseline stroke volume index (r = 0.75, p less than 0.025) and plasma renin activity (r = 0.67, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Calcium stimulates vasopressin release.

The association of acute hypercalcaemia with hypertension has long been known. Its mechanism has remained unexplained, however, since no significant pressor contribution from the renin-angiotensin system or the sympathetic nervous system has been detected. To assess the possible contribution of arginine vasopressin (AVP), we investigated the effect of a 2 h infusion of 2 ml isotonic calcium gluconate (0.46 mmol/ml Ca2+) on the mean blood pressure of anephric (n = 8) or intact (n = 7) rats and the blood pressure response to a specific vasopressin inhibitor (V1). In anephric rats, blood pressure rose by 30 +/- 3 mmHg (mean +/- s.e.m.) and plasma AVP levels rose to 34 +/- 9 pg/ml. In response to injection of the AVP inhibitor, blood pressure fell by 26 +/- 3 mmHg. In intact rats, blood pressure rose by 12 +/- 4 mmHg with plasma AVP levels 14.5 +/- 3.2 pg/ml (normal range 2.2 +/- 1.1 pg/ml), but did not respond consistently to AVP inhibition. Serum calcium levels at the end of the infusion were 25.0 +/- 4.3 mg/dl in anephric and 24.9 +/- 1.2 mg/dl in intact rats. In order to confirm that the calcium ion was indeed responsible for the AVP-dependent changes in blood pressure, another group of anephric rats (n = 8) received a 2 h infusion of CaCl2 (0.46 mmol/ml Ca2+) and exhibited a blood pressure rise of 35 +/- 3 mmHg, which responded to the AVP inhibitor with a blood pressure fall of 22 +/- 3 mmHg. Moreover, prior treatment with indomethacin greatly attenuated the pressor effect of calcium infusion and prevented the rise of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Central alpha-adrenoceptors during the development of hypertension in rats on high and low salt intake.

Our purpose was to investigate the binding characteristics of central alpha-adrenoceptors during the early stages of the development of hypertension in rats on high and low salt (NaCl) intake. We measured alpha 1-[( 3H]prazosin) and alpha 2-[( 3H]rauwolscine) binding in membranes of the hypothalamus and medulla oblongata of six groups of young Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and subtotally nephrectomized WKY (SN) rats with mean arterial blood pressure (MAP) ranging from normotensive to hypertensive levels after 1 week of salt restriction or loading. In the hypothalamus the SN-high salt rats and both SHR groups had elevated alpha 1-number but there was no change in alpha 2-number. Moreover, MAP was positively correlated with mean hypothalamic alpha 1-number in the six groups. In the medulla oblongata alpha 1-number was unaffected. However, high salt diet influenced medullary alpha 2-binding in the opposite manner in WKY rats versus SN rats and SHR. In these latter groups the affinity was increased and the number decreased in response to high salt intake. Furthermore, a positive correlation between MAP and mean alpha 1:alpha 2 ratio existed in both the hypothalamus and the medulla of the six groups. The data suggest that hypothalamic alpha 1-binding capacity was increased in SHR due principally to a genetic condition which is mimicked by salt loading in the SN rats. Medullary alpha 2-adrenoceptors of WKY, which remained normotensive despite salt loading, responded differently to high salt intake than those of the SN and SHR, whose blood pressure rose significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

How does salt raise blood pressure? A hypothesis.

Existing data in the literature indicate that alpha 2-adrenergic receptor agonists have a profound hypotensive action, that sodium attenuates the affinity of alpha 2-adrenergic receptors for agonists, that the location of these receptors in the central nervous system is mainly at the sites of cardiovascular regulation, and that these sites exert a constant tonic inhibition of sympathetic vasoconstrictor tone. This article proposes the theory that sodium exerts its hypertensive action by decreasing the state of affinity of the alpha 2-adrenergic receptors of the central nervous system for locally occurring agonist neurotransmitters, which results in disinhibition of sympathoinhibitory neurons and leads to the hyperadrenergic state characteristic of salt-induced hypertension.

Adrenergic Fibers↗
PubMed1986

Hypertensive effect of a bradykinin antagonist in normotensive rats.

The purpose of these experiments was to study the possible contribution of bradykinin to normal blood pressure maintenance. The bradykinin analogue B4146, a competitive antagonist-partial agonist of bradykinin, was used in three groups of normotensive unanesthetized Wistar rats. Two intra-aortic injections of B4146 (1 mg in 0.2 ml of dextrose) were given 5 minutes apart (i.e., well after return of blood pressure to baseline, which occurred within 68 +/- 19 seconds). One group had been pretreated with the angiotensin converting enzyme inhibitor HOE 498, 1 mg/kg (Hoechst), and one received only dextrose as the first injection to serve as controls. The bradykinin antagonist produced an average increase in mean arterial pressure of approximately 13 mm Hg for all groups. In five animals, however, the first injection of B4146 produced a hypotensive effect, whereas the second one consistently produced a rise in blood pressure. Pretreatment with the angiotensin converting enzyme inhibitor did not affect the magnitude of the subsequent blood pressure increase in response to B4146. Since smaller doses of B4146, sufficient to block exogenous bradykinin, do not cause changes in normal blood pressure, we conclude that endogenous bradykinin does contribute to normal blood pressure maintenance, but its effect can be demonstrated only if very high doses of its antagonist are injected, maybe because a high concentration of the compound is necessary to displace not only circulating but possibly tissue receptor-bound bradykinin as well.

Animals↗
PubMed1986

Vasodepressor role of endogenous bradykinin assessed by a bradykinin antagonist.

This study was designed to examine the contribution of bradykinin to the depressor effect of different antihypertensive drugs in two-kidney renovascular hypertensive rats, using a new specific antagonist of bradykinin. First, the inhibitory capacity of this peptide for exogenously injected bradykinin (75-200 ng) was tested. An inhibition of the vasodepressor action of bradykinin by over 50% was found when the bradykinin inhibitor was infused at a rate of 40 micrograms/min, with little difference at higher rates of infusion. This inhibitor then was infused in three groups of renovascular hypertensive rats after their blood pressure had been decreased by pretreatment with the converting enzyme inhibitor enalapril (MK 421), saralasin, or sodium nitroprusside, respectively. Infusion of the inhibitor produced an immediate 30% increase in blood pressure only in the enalapril-treated group. These results indicate that bradykinin is involved in the decrease of blood pressure produced by converting enzyme inhibition in experimental renovascular hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

The adrenergic system and the release and pressor action of vasopressin.

We studied the effect of various adrenergic components on vasopressin in groups of anephric rats. Pharmacological interventions included alpha 1-, alpha 2-, and beta-adrenergic receptor blockade and infusions of sodium nitroprusside to achieve a baseline blood pressure fall similar to that obtained by alpha 1-blockade, followed by hypertonic saline infusion to stimulate vasopressin release and administration of a specific V1 vascular vasopressin inhibitor to test the degree of blood pressure dependency on vasopressin. The combined hypotensive and osmolar stimuli of nitroprusside followed by hypertonic saline led to the highest level of plasma vasopressin (104 +/- 17 pg/ml, p less than 0.01) but only a 7 +/- 1 mm Hg fall in blood pressure in response to the vasopressin inhibitor. Rats subjected to alpha 1-blockade and saline infusion had the largest blood pressure reduction in response to the vasopressin inhibitor (43 +/- 5 mm Hg, p less than 0.001), despite a modest rise in vasopressin levels (18 +/- 2 pg/ml). Other pharmacological maneuvers produced intermediate responses in terms of vasopressin release and blood pressure response to the vasopressin inhibitor. There was no correlation between vasopressin levels achieved by each maneuver and the magnitude of blood pressure reduction in response to the vasopressin inhibitor. We conclude that 1) plasma levels of vasopressin under these conditions do not permit an accurate estimate of the magnitude of its pressor contribution to the maintenance of a given blood pressure level, which can be demonstrated only by the depressor response to a vasopressin inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗