To characterize alterations in gene expression which may occur during the development of compensated left ventricular pressure overload hypertrophy (CH) and the transition to decompensated congestive ...heart failure (DH), differential RNA display was used to compare mRNA transcripts from sham operated, 4-week, and 8-week thoracic aorta banded guinea-pigs. Of several regulated transcripts chosen for analysis, one was identified by nucleotide sequence homology as titin, a sarcomeric cytoskeletal protein. By differential display and comparative PCR, titin transcripts were increased in CH and then declined in DH. Comparative PCR of desmin and tubulin demonstrated increased mRNA levels for these cytoskeletal proteins in CH and DH. Western analysis showed associated increases in titin (DH) and desmin (CH and DH) protein expression but no increase in tubulin protein. Isolated Langendorff cardiac mechanics failed to reveal functional differences in either hypertrophy phenotype when microtubules were depolymerized (colchicine 10
−6
m). In summary, the major cytoskeletal proteins are differentially regulated in LV pressure overload hypertrophy and failure. Neither the level of β-tubulin or its polymerization state appear to affect LV function in this model of cardiac hypertrophy.
3-Diazo-4-oxocoumarins absorb in the deep ultraviolet (DUV) and upon photolysis undergo a Wolff rearrangement in aqueous environments to afford carboxylic acid photoproducts that are transparent in ...the DUV. Because this photochemical reaction transforms a base insoluble chromophore into a base soluble one, it may be exploited for the design of photolithographic materials. Examples of 5-, 6-, and 7-substituted 3-diazo-4-oxocoumarins have been synthesized and the reactivity of the corresponding photogenerated ketenes has been studied. For most chromophores, the rate of ketene hydrolysis was found to correlate with the calculated charge on the ketenyl carbon. 3-Diazo-4-oxocoumarins bearing electron-donating substituents in these positions demonstrate the lowest reactivity and therefore show the most promise for lithographic materials.
The purpose of this study was to determine whether genetically obese Zucker rats have higher arterial pressures than lean littermates on normal and high sodium intakes. Mean arterial pressure was ...directly measured in chronically instrumented Zucker rats (six lean weight, 345.8 +/- 8.0 g and five obese 529.0 +/- 6.2 g) for 2 weeks on both a normal (2 meq sodium/day) and high (6 meq sodium/day) sodium intake (7 days each). In addition, daily heart rate, water intake, urine output, urinary sodium excretion, urinary potassium excretion, and weekly fasting plasma insulin levels were measured. Obese rats exhibited significantly lower heart rate and greater water intake and urine output compared with lean rats whether maintained on control or high sodium intakes. Urinary sodium excretion, however, was identical in lean and obese rats throughout the experiment. Fasting plasma insulin levels in obese rats were seven times greater than those in lean rats. When the rats were maintained on a 2 meq/day sodium intake, mean arterial pressures obtained from the two groups were similar: 103 +/- 1 versus 106 +/- 1 mm Hg (lean versus obese). An increase in sodium intake did not significantly affect mean arterial pressure in either group: 101 +/- 1 versus 105 +/- 1 mm Hg (lean versus obese). These results indicate that at 12-14 weeks of age, male obese Zucker rats do not exhibit higher resting arterial pressures than lean littermates when maintained on normal or high sodium intake.
The objective of this study was to determine if ablation of the lateral parabrachial nucleus (LPBN) would prevent angiotensin II-induced hypertension in rats. Thirteen male Sprague-Dawley rats were ...studied. Bilateral electrolytic lesions in the LPBN were produced in six rats; the remaining seven rats were subjected to sham lesion surgery only. All rats were instrumented with vascular catheters and housed in metabolism cages. Daily measurements during the 16-day protocol included arterial pressure, heart rate, water intake, urine output, and urinary sodium excretion. Periodically throughout the protocol depressor responses to ganglion blockade and to blockade of V1-type vasopressin receptors also were measured. The protocol was divided into three control-period days, 10 days of continuous (24 hr/day) angiotensin II infusion (10 ng/min i.v.), and three recovery-period days. There were no significant differences between the two groups of rats for any variable during the control period. During angiotensin II infusion, sham-lesion rats exhibited a progressive increase in arterial pressure and the depressor response to ganglion blockade and a decrease in urinary sodium excretion. No other variable was significantly changed. In rats with LPBN lesions, arterial pressure was significantly increased only on days 1 and 3 of angiotensin II infusion. No other variable was affected. It was concluded that ablation of the LPBN in rats prevented sustained hypertension during intravenous infusion of angiotensin II by interfering with neurogenic pressor mechanisms normally activated by the peptide.
Initial experiments demonstrated that a 1-h infusion of 10 ng/min angiotensin II (ANG II) into rats causes an increase in plasma aldosterone concentration (PAC) and that chronic administration of ...aldosterone alone to rats on increased sodium intake causes hypertension. We therefore hypothesized that a portion of the hypertensive effect of chronic ANG II infusion is accompanied by and dependent on chronic release of aldosterone. To test this hypothesis, 10 ng/min ANG II or saline was infused into chronically instrumented rats housed in metabolism cages. Fifteen rats were maintained on a high sodium intake (6 meq/day); 10 received ANG II and 5 received saline. Ten other rats were maintained on a normal sodium intake (2 meq/day); five received ANG II and five received saline. PAC was measured using a commercial radio-immunoassay kit. Mean arterial pressure (MAP), heart rate, water intake, urine output, and urine electrolytes were measured daily during 3-day control, 16- or 28-day infusion, and 4-day recovery periods. Compared with saline-infused rats, ANG II-infused rats on high sodium intake had normal values for all variables except MAP, which was significantly elevated during ANG II infusion. In the normal sodium group, none of the variables were consistently different during ANG II infusion compared with control. These results suggest that ANG II-induced hypertension in the rat is sodium dependent, that plasma aldosterone does not play a major role in ANG II-induced hypertension in the rat, and that a small chronic increase in circulating ANG II does not necessarily lead to a detectable sustained increase in PAC.
This study was designed to investigate the effects on water drinking of acute and chronic increases in circulating angiotensin II (ANG II) concentrations in rats. Experiments were conducted in male ...Sprague-Dawley rats chronically instrumented with femoral arterial and venous catheters and permanently housed in metal metabolism cages. ANG II was infused intravenously either acutely (30 min-2 h) or chronically (3 days) in a dose range of 10-60 ng/min. In no instance did such infusions cause a statistically significant increase in water intake. Other experiments examined the influence of ANG II (10 ng/min iv) on drinking elicited by infusion of hypertonic sodium chloride (1.5 M at 3.5 microliters/min). ANG II administration did not increase drinking to a hypertonic saline stimulus or lower the osmotic threshold for drinking. Nitroprusside (12 micrograms/min) was infused for 30 min to produce hypotension and drinking. Water intake associated with this stimulus was not changed by blocking ANG II formation with enalapril (2 mg/kg iv) or by concomitant infusion of ANG II (10 ng/min iv). Finally, plasma ANG II concentrations were measured before and after 1-h intravenous infusion of saline or ANG II to determine the levels of circulating ANG II produced by the infusion rates used here. It is concluded that the range of circulating ANG II concentrations found under most physiological conditions in rats does not directly stimulate drinking or participate importantly in osmotic or hypotension-induced drinking.
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