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Biomedical subjects

A Borghetti

Publications and source records attributed to A Borghetti.

At least 73 records · Page 4Linked to original sources

Increased sensitivity to protein kinase C activation in aortas of spontaneously hypertensive rats.

The aortic muscle of spontaneously hypertensive (SHR) and normotensive control (WKY) rats was stimulated with phorbol esters and the contractile response was measured as isometric tension. Phorbol esters are known activators of protein kinase C. The aortas of SHR were characterized by the following distinct alterations in the response to phorbol myristate acetate: (1) increased sensitivity: half-maximal force was achieved at 62 +/- 6 nmol/l phorbol myristate acetate in SHR and 105 +/- 8 nmol/l in WKY; (2) increased contractility: the maximal force developed by phorbol myristate acetate was greater in SHR aortas (1.9 +/- 0.3 versus 1.6 +/- 0.2 g in WKY) compared with the decreased contractility generated with noradrenaline and high levels of potassium; (3) decreased dependency on extracellular calcium for half-maximal tension: in the presence of 3 mumol/l phorbol myristate acetate 50% of maximal force was attained at 21 +/- 8 mumol/l extracellular calcium compared with 49 +/- 9 mumol/l in WKY; (4) diminished relaxation in response to excess extracellular calcium: phorbol myristate acetate-precontracted WKY aortas began to relax when calcium was raised above 4 mmol/l in the bath and relaxation reached 51% at 8-10 mmol/l. Relaxation was almost absent in SHR (3-7%). Hence, there is an abnormality in the response to protein kinase C activation by phorbol esters in SHR vascular smooth muscle. Intracellular calcium appears to be involved. Studies of protein kinase C will prove important in understanding vascular smooth muscle function in normal and abnormal states.

Animals↗

The vasodilator effect of human atrial natriuretic factor (99-126) on human omental arteries.

The effect of synthetic human atrial natriuretic factor [ANF-(99-126)] on human omental arteries was investigated. The compound produced concentration-dependent relaxation, 10, 50 and 90% of maximum effect being observed at about 1, 10 and 100 nmol/l, respectively. These concentrations are considerably higher than those measured by radio-immunoassay in human plasma, even under extreme conditions (0.001-0.3 nmol/l). Therefore, ANF can dilate human resistance-size arteries, but whether it does so under physiological conditions has not been established.

Adult↗

Myoplasmic Ca2+-force relationship studied with fura-2 during stimulation of rat aortic smooth muscle.

The intracellular Ca indicator fura-2 was used for simultaneous measurements of intracellular free Ca (Ca2+i) and force in arterial smooth muscle. Rat aortic medial rings were submitted to fluorometry in a geometrical arrangement resembling that of adherent cell layers. A rigid force-transducing system served to immobilize the tissue and record the developed force quasi-isometrically. Stimulation was performed with norepinephrine (NE), KCl depolarization (high K), and a nonfluorescent Ca ionophore (ionomycin) at varying extracellular Ca concentrations. The following facts were observed. NE, high K, and ionomycin increased tension along with fura-2-reported Ca2+i; under any circumstances tension was Ca2+i dependent and could be varied by manipulating Ca2+i. However, NE and high K determined a parallel increase in the effectiveness of Ca2+i in comparison with the simple ionophore, i.e., they increased the force-to-Ca2+i ratio. NE and high K produced half-maximal tension at fura-2 estimated Ca2+i of 0.10 and 0.13 microM, whereas ionomycin required 0.6 microM to achieve the same amount of force. It is inferred that Ca2+i is a determinant of vascular contraction, but some results suggest the existence of factors that sensitize the contractile machinery to Ca.

Animals↗

Dietary sodium change in primary aldosteronism. Atrial natriuretic factor, hormonal, and vascular responses.

Atrial natriuretic factor (ANF) may be physiopathologically involved in several clinical conditions including human hypertension. However, few data are available regarding this putative hormone and its relationship to aldosterone, blood pressure, and vascular responsiveness to alpha-adrenergic receptor stimulation in primary aldosteronism, a volume-expanded, low-renin model of human hypertension. For this reason, the behavior of supine and upright plasma ANF as related to aldosterone, blood pressure, and forearm alpha-adrenergic sensitivity (plethysmographic technique) to intra-arterial norepinephrine infusion was studied in eight patients with primary aldosteronism (five with adenomas, three with hyperplasia) before and at the end of two sequential 1-week low (20 mmol/day) and high sodium (200 mmol/day) diet periods. Basal, predict ANF concentrations decreased and increased after low and high sodium intakes, respectively. Furthermore, highly significant postural ANF decrements after 1 hour of standing occurred with each diet, although they were lower after the low than after the high sodium diet. Plasma aldosterone, either supine or upright, was insensitive to dietary sodium manipulations, suggesting the absence of ANF-mediated control of aldosterone secretion in our patients. In spite of about twofold higher ANF concentrations during the high than during the low sodium diet, forearm vascular sensitivity to intra-arterial norepinephrine infusion did not change during the study. Furthermore, systemic arterial blood pressure rose to a highly significant extent after dietary sodium content was increased, thus casting doubt on a role for ANF as an endogenous long-term modulator of systemic blood pressure and peripheral alpha-adrenergic sensitivity in patients with primary aldosteronism.

Adult↗

Physiological stimuli to atrial natriuretic peptide secretion in normal humans.

We tested the response of plasma atrial natriuretic peptide (ANP) levels to the following physiological stimuli: postural changes; head-out water immersion; and physical exercise. Plasma ANP (p-ANP) levels were assessed by a specific, sensitive radio-immunoassay. Plasma ANP rose significantly when posture shifted from upright to recumbent for 1 h, but fell again to basal values after 10 min standing. Circadian variations did not affect the posture study. Head-out water immersion produced a prompt and remarkable (sevenfold) increase in p-ANP, with a plateau reached after 1 h and held until the end of the experiment (2 h). Plasma ANP levels were measured in 10 normal subjects performing supine treadmill exercise at 50% of maximum aerobic capacity for 30 min. Plasma ANP rose from baseline supine values after 15 min exercise, and remained elevated during the following 15 min exercise. During the recovery phase ANP showed a trend towards baseline values, with a 38% decrease attained after 30 min. We propose that the above tests could be used as ANP-stimulating manoeuvres in physiological and clinical conditions in man.

Adult↗

Adrenal response in the pathogenesis of arterial hypertension in workers exposed to high noise levels.

Some neuroendocrine parameters known as stress indices were examined in two groups of healthy male workers in a glass factory: the first group (60 subjects) was exposed to high environmental noise levels [greater than 90 dB(A)]; the second group (52 subjects) was exposed to low noise levels [less than 78 dB(A)]. Subjects with histories of cardiovascular diseases or high arterial pressure were excluded from the study. In both groups serum catecholamines and cortisol, and urinary vanilmandelic and homovanillic acids were evaluated at the beginning and middle of morning and afternoon work-shifts, by high performance liquid chromatography with electrochemical detection. Norepinephrine, epinephrine and vanilmandelic acid were significantly increased (P less than 0.01) during work-shifts in the group exposed to 90 dB(A), compared with baseline levels and also with catecholamine levels in the group exposed to 78 dB(A). Serum dopamine, cortisol and homovanillic acid showed no significant differences. The increased stimulation of the sympatho-adrenal system in response to high and prolonged noise exposure might lead to an abnormal response of the cardiovascular system with increasing arterial pressure values.

Adrenal Glands↗

The mechanism of Ca2+i increase in blood cells of spontaneously hypertensive rats.

Cytoplasmic free calcium (Ca2+i) is increased in platelets and lymphocytes of spontaneously hypertensive rats (SHR) and, to a lesser extent, in essential hypertensive patients. In this study, a method was devised to evaluate cellular Ca fluxes and the cellular Ca buffering power by means of the intracellular Ca indicator Quin-2. Ca influx was measured under conditions of Ca-pump inhibition, either by vanadate or ATP depletion. Lymphocytes of 5-month-old SHR were compared with those of normotensive Wistar-Kyoto rats (WKY). In both strains, the Ca entry rate and the cellular buffering capacity were higher in vanadate-treated than in ATP-depleted cells. SH rats exhibited a higher Ca influx and a greater intracellular Ca buffering power when vanadate was used to stop the Ca pump; these differences, however, were abolished in ATP-depleted lymphocytes. It is suggested that Ca entry in lymphocytes is ATP-dependent. Accelerated Ca entry in SHR can account for the previously reported higher levels of intracellular free Ca.

Adenosine Triphosphate↗

Similarities of essential and spontaneous hypertension. Volume and number of blood cells.

Spontaneously hypertensive rats have long been used as an animal counterpart of human essential hypertension. The validation of this strain as a model rests mainly on the "clinical" similarity of the two syndromes, but it has scarcely been founded on numerical comparison of measurable parameters. We investigated three hematological indexes previously recognized to be altered in spontaneously hypertensive rats: the single-cell volume of erythrocytes, the single-cell volume of platelets, and the erythrocyte number. Erythrocyte volume was lower by 7%, platelet volume was higher by 12%, and erythrocyte count was higher by 22% in spontaneously hypertensive rats in comparison with Wistar-Kyoto controls. More unexpectedly, it was found that erythrocyte volume is lower by 2%, platelet volume is higher by 3%, and erythrocyte number is higher by 6% in essential hypertensive subjects when compared with normotensive healthy subjects. These results, combined with previously reported blood cell alterations in subjects and rats, reinforce the evidence of a biological similarity between essential and spontaneous hypertension.

Animals↗