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Biomedical subjects

R Garcia

Publications and source records attributed to R Garcia.

At least 325 records · Page 18Linked to original sources
PubMed1988

Alternating non-cross-resistant chemotherapy for metastatic hormone-independent breast cancer.

A phase II clinical trial was designed to apply the treatment strategy of alternating non-cross-resistant chemotherapy regimens to patients with metastatic estrogen-receptor negative or hormone-refractory breast cancer. Twenty-six patients received Adriamycin and cyclophosphamide alternating at 3-week intervals with the combination of vinblastine, mitomycin-C, and 5-fluorouracil (5-FU). Toxicity was moderately severe. Two patients developed grade 2 and three developed grade 1 stomatitis. A single patient developed a WBC count of less than 1000/mm3, whereas five had a lowest recorded WBC count of 1,000-1,999/mm3. Two patients displayed thrombocytopenia of less than 50,000/mm3, one in conjunction with a fatal hemolytic-uremic syndrome. There were six complete and eight partial responses (PRs) for an objective response rate of 54% (64% of fully evaluable patients). The median survival after onset of protocol therapy was 13.3 months. These results are no better than those reported for other Adriamycin-containing regimens.

Adult↗
PubMed1988

The atrial natriuretic factor in hypertension.

Plasma immunoreactive atrial natriuretic factor (IR-ANF) concentration measured by radioimmunoassay after extraction on Sep-Pak cartridges was studied in 64 control normotensive subjects, 25 patients with labile essential hypertension, 67 patients with mild essential hypertension (diastolic pressure between 90 and 105 mm Hg and no left ventricular hypertrophy) and 9 patients with moderate to severe essential hypertension (diastolic pressures between 105 and 120 mm Hg). An additional group of 16 patients under medication but without effective control of their blood pressure and with diastolic pressure above 110 mm Hg also was studied. Results show that plasma IR-ANF concentrations are within normal range in patients with labile, mild, and moderate hypertension. In view of the reported increased right and left atrial pressures and distension in patients with mild and moderate hypertension, these findings strongly suggest a state of hyporesponsiveness of the atria to release ANF.

Animals↗
PubMed1988

Atrial natriuretic factor: specific binding to renal glomeruli during the development of two-kidney, one clip hypertension in the rat.

Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit and renal glomerular ANF receptors were studied during the development of hypertension in two-kidney, one clip (2-K, 1C) rats and were compared with normotensive controls. Plasma ANF was elevated in the 2-K, 1C group in all stages of hypertension, even after 3 weeks when BP, although higher than in sham-operated animals, had not yet reached arbitrarily-set hypertensive levels. At this time, hematocrit was higher in the hypertensive rats than in the controls, but the difference later disappeared. Lower atrial ANF concentrations were observed in the 2-K, 1C group at week 3, but only in the right atrium. No difference in ANF levels was noted in either the left or right atrium between hypertensive and normotensive animals 5 and 7 weeks after clipping. The glomerular ANF receptor population was markedly smaller in the clipped left kidney of 2-K, 1C rats during all stages of hypertension, and in the untouched right kidney at 5 and 7 weeks after surgery, but was larger in the non-clipped right kidney in the pre-hypertensive phase (3 weeks). It is concluded that receptor density changes during the evolution of high BP in the 2-K, 1C Goldblatt model of experimental hypertension. Our data suggest that the increases and decreases in density of renal glomerular ANF receptors may play a role in the differential handling of sodium by the clipped and non-clipped kidney during the various stages of development of 2-K, 1C hypertension in the rat.

Animals↗
PubMed1988

Glomerular ANF receptor regulation during changes in sodium and water metabolism.

The concentration of atrial natriuretic factor (ANF) in atria and plasma was investigated in relation to the regulation of renal glomerular ANF receptors in the rat during changes in water and sodium intake. A decrease in plasma immunoreactive ANF (IR-ANF) was observed after 4 days of water deprivation or after 1 wk on a low-sodium diet, whereas animals offered 1% NaCl in their drinking water had elevated plasma ANF values. Atrial IR-ANF was lower in water-deprived and higher in sodium-restricted rats than in their respective controls. A low-sodium intake or water deprivation increased the density of glomerular ANF receptors, whereas the inverse occurred with a high-salt consumption. It is concluded that an inverse correlation exists between ANF plasma concentration and renal glomerular ANF receptor sites.

Animals↗
PubMed1988

Glomerular atrial natriuretic factor receptors during rehydration: plasma NH2- and COOH-terminal levels.

Atrial natriuretic factor (ANF) concentration in atria and plasma was investigated in relation to the density and affinity of renal glomerular ANF receptors during water deprivation and rehydration in the rat. Immunoreactive (IR) ANF-(99-126) was lower during water deprivation (4.2 +/- 0.5 fmol/ml) than in normally hydrated animals (10 +/- 1.5 fmol/ml); NH2-terminal IR ANF-(1-98) was also lower in water-deprived rats (75 +/- 2.4 fmol/ml) than in the controls (708 +/- 105 fmol/ml). These decreased plasma COOH- and NH2-terminal ANF concentrations were accompanied by significantly higher hematocrit, serum osmolality, and Na+ values. The renal glomerular ANF receptor population was greater in water-deprived animals than a control animals. After rehydration, IR ANF was elevated within 1 h and reached control values after 6 h. Hematocrit, serum osmolality, and Na+ did not normalize until 48, 6, and 24 h, respectively. The renal glomerular ANF receptor population, which was markedly higher in water-deprived rats, gradually declined after rehydration, so that no difference was observed with the control group 24 h later.

Animals↗
PubMed1988

Renal glomerular atrial natriuretic factor receptors in one-kidney, one clip rats.

One-kidney, one clip (1K1C) hypertension is often associated with an expanded plasma volume and (once the arterial clip is removed) with natriuresis. Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit, and renal glomerular ANF receptors were therefore studied in 1K1C rats and in their normotensive uninephrectomized controls before and after unclipping. Six hours after removal of the clip, BP was normal in the 1K1C group and plasma ANF presented a sharp decline but was still significantly higher than in the normotensive controls, with a slight difference being evident 24 hours after unclipping. Hematocrit was lower in the 1K1C rats than in their control counterparts, but this difference tended to disappear once the clip was removed, indicating a contraction of plasma volume in these unclipped 1K1C animals. The renal glomerular ANF receptor population was markedly smaller in 1K1C rats than in the uninephrectomized controls but showed a twofold increase in number and affinity 24 hours after unclipping. It is concluded that the up-regulation and enhanced affinity of glomerular ANF receptors (probably secondary to the decrease in plasma levels of ANF) may contribute to the natriuresis reported in hypertensive 1K1C animals on removal of the arterial clip.

Animals↗
PubMed1988

Atrial natriuretic factor release by angiotensin II in the conscious rat.

Since it was previously reported that atrial natriuretic factor (ANF) may exert an inhibitory effect on renin release, the existence of an Angiotensin II (Ang II)-ANF feedback mechanism was investigated. Male rats were infused intraperitoneally for 7 days with either saline, a nonpressor dose of Ang II (200 ng/kg/min), or a pressor dose (800 ng/kg/min) of Ang II. Systolic blood pressure, plasma ANF, 24-hour urinary sodium excretion, urine volume, and water intake were measured. A significant increase in plasma ANF was observed in the group with a pressor response (blood pressure rose from 89.0 +/- 3.9 to 136.7 +/- 11.4 mm Hg; ANF rose from 36.8 +/- 4.9 to 92.7 +/- 17.7 pg/ml). There was no significant time effect on 24-hour sodium excretion, urine volume, and water intake in both Ang II-infused groups. In a second set of experiments, male rats were infused intravenously for 60 minutes with either saline, a nonpressor dose of Ang II (16 ng/kg/min), or a pressor dose (800 ng/kg/min) of Ang II. Left ventricular end-diastolic pressure, right atrial pressure, and mean arterial pressure were monitored. There was a significant increase in plasma ANF and left ventricular end-diastolic pressure only with the pressor dose (blood pressure rose from 85.0 +/- 6.1 to 140.0 +/- 5.5 mm Hg; ANF rose from 22.6 +/- 6.0 to 108.3 +/- 47.7 pg/ml; left ventricular end-diastolic pressure rose from 5.3 +/- 5.7 to 20.8 +/- 7.9 mm Hg). No significant modification of right atrial pressure was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1988

Glomerular and vascular atrial natriuretic factor receptors in saralasin-sensitive and -resistant two-kidney, one-clip hypertensive rats.

We have investigated whether there is a relation between renin dependency of two-kidney, one-clip (2K1C) hypertensive rats and the density of renal glomerular and vascular atrial natriuretic factor (ANF) receptors. Conscious 2K1C rats with blood pressure of 150 mm Hg or higher were classified according to their sensitivity to the blood pressure-lowering effect of the angiotensin II antagonist saralasin. Both hypertension groups had lower body weights and greater relative heart weights than normotensive controls. Hematocrit was lower and plasma volume higher in saralasin-resistant animals than in either saralasin-sensitive or control rats. Plasma renin activity was higher in the saralasin-sensitive group than in the resistant rats. Plasma ANF concentration was greater in saralasin-resistant than in either normotensive or saralasin-sensitive animals. ANF was reduced in both atria of saralasin-resistant 2K1C animals but only in the left atrium of the sensitive group. Both hypertensive groups showed an increased ventricular ANF concentration. The number of glomerular ANF binding sites was significantly lower in the clipped kidney of both hypertensive groups. This lower density of binding sites was accompanied by an increased affinity. In saralasin-sensitive rats, the density of glomerular ANF receptors in the nonclipped kidney was significantly higher than in the controls. Saralasin-resistant rats exhibited a decreased number of vascular ANF binding sites in both mesenteric arteries and aorta. We conclude that through modulation of its glomerular and vascular receptors, ANF may contribute to the differential sodium handling of saralasin-sensitive and -resistant 2K1C hypertensive rats and to the reduced vascular responsiveness to ANF observed in the saralasin-resistant hypertensive rats.

Animals↗
PubMed1988

ANF in experimental congestive heart failure.

The plasma and cardiac levels of immunoreactive (IR) atrial natriuretic factor (ANF) were measured during the entire lifespan of cardiomyopathic hamsters, which eventually develop spontaneous congestive heart failure, and were correlated with immunohistochemical, ultrastructural, and immunocytochemical changes in the secretory apparatus of atrial and ventricular cardiocytes. Plasma IR-ANF rose in the early stages of the disease, reached a maximum in moderate heart failure, and declined thereafter but remained above control values. The peptide decreased constantly in the atria during the evolution of the disease but increased markedly in the ventricles. Its highest levels were found in the inner half of the left ventricle. In atrial cardiocytes, the size and complexity of the Golgi complex increased with the progression of the disease, whereas the number, size, and IR-ANF content (as assessed by the immunogold technique) of secretory granules decreased constantly. In ventricular cardiocytes, the size of the Golgi complex increased, and typical secretory granules were present in approximately 20% of these cells, regardless of their localization in the myocardium. The results suggest that stimulation of ANF secretion in atrial cardiocytes leads to a dissociation between synthesis and release, the latter being maximal according to ultrastructural and immunocytochemical criteria. In ventricular cardiocytes, the same stimulation culminates in increased synthesis and the possibility of release via two pathways: one constitutive, the other regulated. Thus, the elevated plasma levels of IR-ANF in congestive heart failure may be derived from secretion by both atrial and ventricular cardiocytes.

Animals↗
PubMed1988

An evaluation of Gambusia affinis and Bacillus thuringiensis var. israelensis as mosquito control agents in California wild rice fields.

The mosquito control potential of the mosquitofish and Bacillus thuringiensis var. israelensis (Bti) were evaluated in experimental wild rice fields in Lake County, California. Fields were assigned one of six treatment: control, 1.1 kg/ha G. affinis, 3.4 kg/ha G. affinis, Bti only (6 kg/ha Vectobac granules), 1.1 kg/ha G. affinis plus Bti and 3.4 kg/ha G. affinis plus Bti. Gambusia affinis, at both release rates, significantly reduced the mosquito population at densities exceeding 100 fish/minnow trap. Treatments with Bti significantly reduced larval population; however, the populations in the fields without fish rebounded to pretreatment levels within two weeks. In fields stocked with G. affinis and treated with Bti, populations remained low after Bti treatment. Nontarget populations of arthropods were significantly lower in fields stocked with G. affinis than in fields without fish on one or more sampling dates.

Agriculture↗
PubMed1988

[Concentration of the atrial natriuretic factor in the atria and blood plasma in the development of hypertension in spontaneously hypertensive rats].

The contribution of atrial natriuretic factor to the development of spontaneous arterial hypertension was investigated in rats (the SHR line). Prehypertensive atrial and plasma levels of a natriuretic factor were similar in SHR to those of the control WKY rats. In fully-developed hypertension, the factor content decreases in left-atrial wall and increases in the plasma. It is assumed that elevated arterial blood pressure affects myo-endocrine left-atrial cells, leading to hypersecretion of the natriuretic factor. This kind of secretory response might be an adaptive/compensatory mechanism of blood pressure control.

Aging↗
PubMed1987

Specific binding of atrial natriuretic factor to renal glomeruli in Doca- and Doca-salt-treated rats correlation with atrial and plasma levels.

Since volume expansion and high blood pressure (BP) are known stimuli of atrial natriuretic factor (ANF) release, and since this peptide may be involved in mineralocorticoid escape, we investigated the effects of chronic deoxycorticosterone (DOCA) and DOCA-NaC1 treatment on renal glomerular ANF receptor density and affinity in relation to atrial and plasma ANF levels. An increase in plasma immunoreactive ANF (IR-ANF) was observed both after two and four weeks of treatment. IR-ANF concentrations were elevated in the left atrium only in four-week DOCA treated rats. Administration of the mineralocorticoid alone resulted in a decreased density of glomerular ANF receptors in both time periods investigated. DOCA-NaC1-treated animals presented an increased receptor density during the pre-hypertensive stage (2 weeks) and a reduced density in the later hypertensive period (4 weeks). Receptor affinity in both groups was identical to that in the controls after 2 weeks and was augmented after 4 weeks of treatment. Our data suggest that the down-regulation of renal glomerular ANF receptors during chronic DOCA-NaC1 administration may play a role in the maintenance of high BP in this model of volume-expanded hypertension.

Animals↗
PubMed1987

Correlation between cardiac hypertrophy and plasma levels of atrial natriuretic factor in non-spontaneous models of hypertension in the rat.

We have compared atrial and plasma concentration of atrial natriuretic factor (ANF) in 4 models of non spontaneous experimental hypertension with different pathogenic mechanisms in the rat: two-kidney, one-clip (2-K, 1-C), one-kidney, one-clip (1-K, 1-C), DOCA-NaCl and adrenal regeneration hypertension (ARH) and their respective normotensive controls. All hypertensive groups developed cardiac hypertrophy. In all hypertensive groups plasma ANF was higher than in controls. Atrial ANF concentration was lower in the right and left atrium of 1-K, 1-C rats and in the left atrium of ARH. A good correlation was found between systolic BP and plasma ANF in 2-K, 1-C (r = 0.82; p less than 0.01) and 1-K, 1-C animals (r = 0.70; p less than 0.01). This correlation was less good in DOCA-NaCl (r = 0.41; p less than 0.05) and non existent in ARH (r = 0.28; NS). A negative correlation between plasma ANF and atrial ANF concentrations was found only in the 1-K, 1-C group (r = 0.41; p less than 0.05). A good correlation between plasma ANF levels and cardiac weight was found in all groups: 2-K, 1-C (r = 0.83; p less than 0.01), 1-K, 1-C (r = 0.73; p less than 0.01), DOCA-NaCl (r = 0.69; p less than 0.01) and ARH (r = 0.71; p less than 0.01). We suggest that the release of ANF in experimental hypertension depends of the pathogenesis and could be related either to the level of BP (hence the magnitude of the left ventricular end-diastolic pressure) or to the existence of an expanded blood volume. The correlation between plasma ANF levels and cardiac hypertrophy suggests that ANF could be partially released by the ventricles.

Adrenal Glands↗