Biomedical subjects

T Quesada

Publications and source records attributed to T Quesada.

At least 55 records · Page 3Linked to original sources

PubMed1989

Hemodynamic effects of hypertonic saline in the conscious rat.

The present study examines the role of vasopressin and the sympathetic nervous system on the hemodynamic effects of an infusion of hypertonic saline (NaCl 1.5 M) in conscious rats. The cardiovascular response to hypertonic saline was similar in both untreated and hexamethonium-pretreated rats. Mean arterial pressure increased by 15 mmHg as a consequence of the elevation of total peripheral resistance, while cardiac index was decreased. The administration of an antagonist to the pressor activity of vasopressin in rats with intact reflexes, partially decreased mean arterial pressure and total peripheral resistance and increased cardiac index toward basal values. In contrast, the hemodynamic response to hypertonic saline was totally reverted when the vasopressin antagonist was injected in the hexamethonium-pretreated rats. The results of the present study indicate that the hypertensive response induced by hypertonic saline in conscious rats is due to the vasoconstrictor effects of both vasopressin and the sympathetic nervous system.

Animals↗

PubMed1989

Hemodynamic effects of chronic infusion of rANP in renal hypertensive rats.

The purpose of this study was to evaluate the hemodynamic effects induced by an infusion of synthetic rat atrial natriuretic peptide (rANP, 0.5 micrograms/h iv) during 5 consecutive days in conscious normotensive and two-kidney, one-clip hypertensive (2K,1C) rats. Changes in plasma ANP (pANP) levels and plasma renin activity (PRA) were also determined. The administration of ANP in 2K,1C rats induced a significant decrease in mean arterial pressure (MAP) from 169 +/- 3 to 138 +/- 3, and 149 +/- 3 mmHg by 2 and 5 days of infusion, respectively. This hypotension was accompanied by a significant fall in cardiac index (CI) from 400 +/- 16 to 348 +/- 14 ml.min-1.kg-1 after 2 days of ANP treatment. However, CI returned to the basal levels at the third day, and a significant decrease in total peripheral resistance (TPR) was observed by 3 and 5 days of ANP infusion. The administration of the same dose of ANP in normotensive rats did not induce changes in MAP, but CI decreased (P less than 0.001) transitorily during the first 2 days and returned to control values thereafter. Basal pANP levels were significantly elevated in the hypertensive animals (176 +/- 40 pg/ml) when compared with the normotensive rats (82 +/- 10 pg/ml). The ANP infusion resulted in lower (P less than 0.05) pANP levels in hypertensive (1,017 +/- 234 pg/ml) than in normotensive rats (3,466 +/- 975 pg/ml). PRA did not change in any group during the administration of ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Effects of converting-enzyme inhibitor on hemodynamic actions of ANP in renal hypertensive rats.

In the present study, we have evaluated whether the hemodynamic effects of atrial natriuretic peptide (ANP) infusion in two-kidney, one-clip (2K, 1C) hypertensive rats are mediated by inhibition of the renin-angiotensin system (RAS). Hemodynamic determinations were performed by thermodilution in conscious, chronically instrumented animals. ANP (1.5 micrograms.kg-1.min-1) and converting-enzyme (CE) inhibitor captopril (1 mg/kg plus 1 mg.kg-1.h-1), produced a similar fall of blood pressure through different hemodynamic mechanisms. ANP induced hypotension by decreasing cardiac index (CI; from 337.3 +/- 24.9 to 255.1 +/- 21.3 ml.min-1.kg-1, P less than 0.001), whereas a fall in total peripheral resistance (TPR) was observed during CE inhibition (from 0.568 +/- 0.02 to 0.488 +/- 0.02 mmHg.min.ml-1.kg, P less than 0.05). In addition, the ANP-induced decrease in CI was not significantly modified by previous CE inhibition. Furthermore, the decrease in TPR induced by CE inhibition did not change when CE inhibitor was administered during ANP treatment. The results of the present study indicate that the acute hemodynamic responses to ANP in 2K, 1C hypertensive rats are not mediated through antagonism of the vasoconstrictor actions of the RAS.

Angiotensin II↗

PubMed1988

Vascular and adrenal reninlike activity in chronically diabetic rats.

The aim of this work was to investigate, in an experimental model of diabetes mellitus, the levels of renin activity in vascular and adrenal tissues and their relationship to several circulating renin-angiotensin system components. Rats with chronic (12 weeks) streptozocin-induced diabetes showed a significant decrease in plasma renin activity (PRA), plasma renin concentration, and plasma aldosterone. However, plasma trypsin activatable inactive renin concentration was increased (11.65 +/- 1.40 vs 6.73 +/- 0.57 ng angiotensin I/ml/hr; p less than 0.001), as were aortic reninlike activity (p less than 0.001) and adrenal renin, both in the zona glomerulosa (p less than 0.01) and the fascicular-reticular-medullary portion (p less than 0.001) with respect to an age-matched control group. After bilateral nephrectomy, plasma renin-angiotensin system components (PRA and plasma active and inactive renin concentrations) as well as aortic and fascicular-reticular-medullary renin activity significantly decreased in both control and diabetic rats. However, glomerular renin activity increased in control nephrectomized rats to the levels observed in diabetic animals but did not change in diabetic nephrectomized rats. The parallel changes of aortic and fascicular-reticular-medullary renin activity and plasma inactive renin concentration in diabetes and nephrectomy suggest an interdependent relationship, whereas the increase of glomerular renin activity in diabetic and nephrectomized animals, both with low levels of PRA, suggests the existence of a local autonomic renin-angiotensin system regulated by plasma feedback. Tissue renin-angiotensin system alterations in diabetes could mean that a pathogenic factor is involved in long-term diabetic complications or that only a compensatory physiological process is at work.

Adrenal Glands↗

PubMed1988

Role of prostaglandins in mediating the renal effects of atrial natriuretic factor.

The natriuretic response to the intrarenal administration of atrial natriuretic factor (ANF) is accompanied by an increase in the synthesis of prostaglandins and by a redistribution of renal blood flow from the superficial to the deep cortex. This study was undertaken to define whether prostaglandins mediate the ANF-induced redistribution of renal blood flow and if prostaglandins and renal blood flow redistribution contribute to the natriuretic actions of ANF. In anesthetized dogs, the intrarenal administration of indomethacin (10 micrograms/kg/min) or the intravenous administration of meclofenamate (5 mg/kg) completely prevented the sixfold and twofold increments in urinary prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, respectively; it also abolished the redistribution of renal blood flow to the deep cortex. However, ANF induced a similar natriuresis before (from 53 +/- 17 to 281 +/- 48 microEq/min) and after (from 45 +/- 13 to 273 +/- 60 microEq/min) the administration of prostaglandin synthesis inhibitors. It is concluded that the ANF-induced redistribution of renal blood flow to the deep cortex is prostaglandin-mediated but that neither redistribution nor increased prostaglandin synthesis is an important mediator of ANF's natriuretic action.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Effect of converting enzyme inhibition with captopril on baroreflex sensitivity.

Clinical and experimental data suggest that both Captopril and angiotensin II (AII) reduce baroreflex responsiveness, and the main action of this converting enzyme inhibitor (CEI) seems clear to suppress AII synthesis. The aim of this work is to investigate this striking similarity of effects. We have verified that CEI (4 mg/kg) originates tachycardia significantly lower (P less than 0.001) than that produced in response to a similar hypotension elicited by an unspecific vasodilator: sodium nitroprusside (10-45 micrograms/kg min). CEI SQ 20881 has been reported to increase plasma vasopressin concentrations (AVP); this peptide is also known to modify baroreflex responses and has a small direct negative chronotropic effect. However, our determinations of AVP do not show any difference between the control group and the group treated with Captopril (4.78 +/- 0.87 and 5.26 +/- 0.19 pg/ml respectively). On the other hand, although CEI did not modify the rapid responses of heart rate (HR) to changes of mean arterial pressure (MAP), the decrease of MAP induced by nitroprusside was higher in the group treated with Captopril than in control group; it could mean a baroreflex ability decrease to buffer the hypotension. However, AII elicited a strong impairment of both rapid responses of HR and the buffering of hypotension produced by NP, these actions being suggested as centrally mediated. These results could indicate that the suppression of peripheral AII synthesis and therefore, the lack of pre- and postjunctional sympathetic potentiation owing to this hormone, is responsible for the absence of tachycardia under Captopril treatment.

Angiotensin II↗

PubMed1988

Adrenal and vascular renin-like activity in chronic 'two-kidney, one-clip' hypertensive rats.

In order to study the vascular and adrenal renin angiotensin system in the chronic phase (4 months after clipping) of 'two-kidney, one-clip' hypertension in rats, systolic blood pressure, plasma renin activity, and tissue renin-like activity in both aorta and adrenal have been measured. Renin activity in adrenal gland was studied in both the zona glomerulosa (GLO) and the remainder of the gland. Results showed an increase in vascular renin activity in chronic hypertensive rats. Moreover it was found that GLO of hypertensive rats presented a significant increase in renin-like activity compared with controls (349.43 +/- 43.86 versus 167 +/- 34.25 ng AI/g/20 h, p less than 0.01) and the fasciculata-reticular-medullar (FRM) portion also showed greater renin activity (345.16 +/- 64.36 versus 57.90 +/- 4.83 ng AI/g/20 h, p less than 0.01). The higher levels of vascular and FRM renin-like activity in chronic renal hypertension are probably a consequence of plasma renin increase. This hypothesis is supported by the fact that bilateral nephrectomy in normal rats induces a significant decrease in plasma renin activity and both aortic and FRM renin-like activity. On the other hand the GLO renin-like activity could depend on both plasma renin and local synthesis since bilateral nephrectomy induces an increase in the renin-like activity in this tissue. These data support the idea that aortic and FRM renin are, at least in part, due to plasma renin uptake and GLO renin is an autonomic system.

Adrenal Glands↗

PubMed1987

Role of prostaglandin and angiotensin II in ANP-induced natriuresis.

The aim of the present study was to examine if the natriuresis induced by a dose of ANP that does not alter glomerular filtration rate (GFR) or mean arterial pressure (MAP) is accompanied by changes in renin release urinary excretion of prostaglandins and intrarenal blood flow distribution. It was found that the intrarenal infusion of ANP (8-33) at a dose of 0.05 micrograms/kg min in seven anaesthetized dogs did not produce any change in GFR or MAP, but its natriuretic effect was similar to that induced by a larger dose (0.3 micrograms/kg min, n = 5) that produces significant changes in both MAP and GFR. The natriuresis induced by the lower dose of ANP was associated with a redistribution of RBF to the deep cortical nephrons and with an increase (p less than 0.05) in urinary excretion of prostaglandins E2 and 6 keto-F1 alpha. Renin secretion rate decreased by a 54% (p less than 0.05). The role of angiotensin II (AII) suppression on the natriuresis induced by ANP was examine in another experimental group (n = 6). It was found that the infusion of ANP during fixed intrarenal levels of AII produced a natriuretic effect that was significantly lower (38%) than that produced by the infusion of ANP alone. The results of this study show that the natriuresis induced by ANP is not necessarily produced by an increase in GFR and is associated with a redistribution of RBF to the deep cortex an increase in urinary excretion of prostaglandins and a decrease of renin release. These results also suggest that the natriuretic effect of ANP is partly mediated by the intrarenal suppression of AII.

Angiotensin II↗

PubMed1987

Hemodynamic alterations in chronically conscious unrestrained diabetic rats.

Important cardiovascular dysfunctions have been described in streptozotocin (STZ)-diabetic rats. To determine the influence of these changes on the hemodynamic state and whether insulin treatment can avoid them, different hemodynamic parameters, obtained by the thermodilution method, were studied in STZ-induced (65 mg/kg) diabetic male Wistar rats, as well as in age-control, weight-control, and insulin-treated diabetic ones. All rats were examined in the conscious, unrestrained state 12 wk after induction of diabetes or acidified saline (pH 4.5) injection. At 12 wk of diabetic state most important findings were normotension, high blood volume, bradycardia, increase in stroke volume, cardiac output, and cardiosomatic ratio, and decrease in total peripheral resistance and cardiac contractility and relaxation (dP/dtmax and dP/dtmin of left ventricular pressure curves). The insulin-treated diabetic rats did not show any hemodynamic differences when compared with the control animals. These results suggest that important hemodynamic alterations are present in the chronic diabetic state, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.

Animals↗

PubMed1987

Difference between intracarotid and intravenous infusions of angiotensin II on baroreflex sensitivity and vasopressin release in conscious rats.

A carotid infusion of angiotensin (AII) (10 ng/kg/min) has been found to increase significantly higher mean arterial pressure (MAP) and produces significantly lower bradycardia than AII intravenous infusions at the same dose and rate. Besides, i.v. administration of AII elicits greater impairment on baroreflex sensitivity than carotid infusion of AII does. On the other hand, vasopressin vascular receptor blockade did not modify the baroreflex sensitivity either in the carotid or in the i.v. infusions of AII, and plasma AVP measurements did not change significantly in any group. It clearly indicates that neither AVP nor baroreflex impairment plays any role on the pressor action of AII intracarotid infusions at a low dose. The present results further suggest that baroreflex impairment in rats may unlikely be located in the region irrigated by the carotid artery.

Angiotensin II↗

PubMed1986

Blood pressure control in pithed rat.

In the pithed Wistar rats Captopril (2 mg/kg) decreased the mean arterial pressure (MAP) 21%. Further injection of a specific antagonist decreased the vasoconstrictor action of vasopressin (aAVP, 10 micrograms/kg) an additional 6%. Reversal in the order of drug administration did not change these percentages. The osmotic stimulus evoked by the infusion of hypertonic saline (ClNa 9%, 0.018 ml/min, 2 hr) significantly increased MAP, this increase being almost totally reversed by the aAVP (10 micrograms/kg). These findings suggest a greater role of the renin-angiotensin system than of the vasopressin (AVP) in the maintenance of MAP in the pithed rat; AVP, moreover, can be released by means of an osmotic stimulus.

Animals↗

PubMed1986

Dopamine-beta-hydroxylase activity in plasma, spleen and adrenal gland of streptozotocin-diabetic rats: correlation with cataracts.

In streptozotocin-diabetic rats a large increase in plasma dopamine-beta-hydroxylase activity was observed. This increase returned to control values with sufficient insulin doses (6 I.U/day); lower insulin doses did not allow normal level to be reached, a dose-dependent decrease being observed. Although the glycemia levels in the diabetic state are responsible for the plasma dopamine-beta-hydroxylase, there is no exact ratio between these two parameters when diabetic animals are treated with different insulin doses which suggests not only the clearance of plasmatic dopamine-beta-hydroxylase, but a contribution from exocytotic tissues as well. In the experimental conditions, before cataracts appeared, the animals about to develop opaque lenses showed a greater dopamine-beta-hydroxylase activity than those which were to remain without this complication. After three months in diabetic state, the severity of disease was evident in the animals with cataracts since they showed a significantly higher function of the sympathoadrenal axis, expressed in spleen and adrenal dopamine-beta-hydroxylase activity. Plasma dopamine-beta-hydroxylase, as a minority glycoprotein can be considered a useful parameter of other mannose-terminal glycoproteins without having a well-known function, and also as a high risk protein, the accumulation of which in several places contributes to the complex pathogenic mechanism of diabetes complications.

Adrenal Glands↗

PubMed1985

Sympathoadrenal activity and plasma glucose effects on plasma dopamine-beta-hydroxylase levels in rats.

Plasma dopamine-beta-hydroxylase (DBH) activity is a controversial index of sympathoadrenal function. In our results, the half-life of bovine DBH administered by cardiac puncture to Wistar rats was dependent on plasma glucose values, being 60 min for controls, 96 min for streptozotocin (STZ)-diabetic animals (p less than 0.02) and 33 min for insulin-treated normal rats (p less than 0.01). In experimental situations with low plasma glucose levels, DBH activity was also diminished with respect to controls (glucose: 103.6 +/- 2.2 mg%, DBH: 9.7 +/- 0.5 U/ml). After fasting, glucose was 60.8 +/- 1.5 mg% (p less than 0.001) and plasma DBH 6.4 +/- 0.3 U/ml (p less than 0.001); fasting plus cold exposure also decreased glucose (66.2 +/- 1.4 mg%, p less than 0.001) and plasma DBH (6.7 +/- 0.2 U/ml; p less than 0.001). In both situations, there was an increase in exocytosis from sympathoadrenal tissues; however, no increase in plasma DBH levels was observed, because plasma glucose being diminished it was unable to compete at the catabolic receptor level. When normal plasma glucose levels take place, plasma DBH is essentially constant, poorly reflecting a moderate increase or decrease in exocytosis from tissues, as was the case in our animals with 48 h of cold exposure. When chemical sympathectomy (6-OH-dopamine) or bilateral adrenalectomy was performed there was a compensatory mechanism between them. Plasma DBH does not change significantly in these situations if plasma glucose values are normal. From these results, the most important physiological influence on plasma DBH activity is the glucose plasma levels. Plasma DBH values not being a useful index of sympathoadrenal activity if, at the same time, the plasma glucose levels are not considered.

Adrenal Glands↗

PubMed1985

Dopamine-beta-hydroxylase activity in adrenal gland and spleen of rats after fasting and cold exposure.

Fasting (48 h) results in dopamine-beta-hydroxylase (DBH) release both in adrenal gland and spleen, suggestive of an increase in the activity of these organs. Cold exposure (48 h) produces a dissociation of the sympathoadrenal response. When both stimuli are simultaneously employed, the DBH response suggests the preponderance of the response to fasting. Plasma DBH is decreased in all groups studied, this could be due to its half-life and the splenic DBH depletion.

Adrenal Glands↗

PubMed1985

Effect of captopril on norepinephrine vascular contractility.

In isolated aortic rings and in vitro perfused mesenteric arteries of Wistar rats the vasoconstrictor responses to norepinephrine (NE) were not affected by captopril (2 X 10(-4) M). However, captopril (1 mg/kg i.v.) in pithed Wistar rats attenuated significantly the increases in diastolic blood pressure induced by NE. In pithed rats the effect of captopril on NE diastolic blood pressure responses disappeared either in the presence of an angiotensin II (5 ng X kg-1 X min) infusion or when the rats were previously nephrectomized. These findings suggest that the effect of captopril on vascular responses to norepinephrine is mediated by an inhibition of the renin-angiotensin system and not by an antagonistic effect on alpha-adrenergic receptors.

Angiotensin II↗

PubMed1985

Role of sodium balance on maintenance of blood pressure in the chronic phase of two-kidney, one-clip hypertension.

Blood pressure and sodium balance have been studied after unclipping, nephrectomy and sham operation of ischemic kidney in the chronic phase (16 weeks) of two-kidney, one clip hypertension. In hypertensive rats the fractional excretion of sodium was 85.5 +/- 2.3% and blood pressure (BP) was significantly increased (187.1 +/- 4.5 mmHg, p less than 0.001). Removal of either the constricting clip or ischemic kidney induced a decrease of BP to normal level whereas sham operation did not produce any change. However, rats submitted to these three experimental manipulations showed, at 1, 2, 3 and 4 days, and at 3 weeks, similar changes in sodium excretion. In the groups with unclipping or nephrectomy of ischemic kidney, water intake was less and urine volume smaller than in the sham operated group. These results suggest that a positive sodium balance is not important to maintain hypertension at this stage and that changes in sodium balance, after both unclipping and nephrectomy of ischemic kidney, have no influence in BP normalization.

Animals↗

PubMed1985

Normal hemodynamic parameters in conscious Wistar rats.

The evolution of different hemodynamic parameters with ponderal growth has been studied in conscious Wistar rats. The thermodilution method has been used to determine cardiac output and related variables. The results suggest that, between animal weight and the different hemodynamic parameters, there is a direct proportional relationship to blood volume, mean arterial pressure, cardiac output, stroke volume and total peripheral resistance, and an indirect proportional relationship to heart rate, cardiac index and stroke volume index. Body weight, therefore, plays a major role in hemodynamic determination, this having to be kept in mind when designing the experiment.

Animals↗

PubMed1984

Effect of diabetic hyperglycemia and other sugars on plasma dopamine-beta-hydroxylase activity.

The plasma glycoprotein, dopamine-beta-hydroxylase (DBH), is present in markedly increased amounts in experimental, streptozocin (STZ)-diabetic rats, reaching a maximum at about the first week and maintaining a plateau for several months afterward. High glycemia values are observed simultaneously. Insulin treatment is observed to keep the glycemia and plasma DBH activity values at levels seen in control rats. The heterologous half-life of DBH in STZ-diabetic rats is significantly increased compared with that of control animals. The glucose analogue, 2-deoxy-D-glucose, has a similar effect on plasma DBH activity levels, eliciting high glycemia values. In STZ-diabetic animals, this increase is more significant, as if it were the additive effect of the two sugars. Other sugars that can compete for glycoprotein catabolic receptors can also modulate the plasma DBH activity levels. The lack of effect of galactose on DBH levels, together with the induced increase of DBH by alpha-methyl-D-mannoside and, to a lesser extent, by inulin, suggest an important rate for the mannose/glucose/N-acetyl glucosamine/fructose receptor in the catabolic clearance of DBH from plasma and explain the abnormal values seen for DBH in diabetes mellitus.

Animals↗