José L. Cangiano

Renal Na+ -K+ - ATPase in Weanling and Adult Spontaneously Hypertensive Rats

Abstract The interrelationships among plasma renin activity (PRA, ng AI/ml plasma/hr), aldosterone concentration (ng%), and renal Na+-K4-ATPase activity (μmole PO4/mg protein/hr) were studied in 9 weanling normotensive spontaneously hypertensive rats (SHR), 9 adult hypertensive SHR, and 9 weanling and 9 adult normotensive Wistar-Kyoto rats (WKY). All groups were placed on a normal (0.4% sodium) diet. PRA and plasma aldosterone, measured in samples drawn from the ether-anesthetized rat, were higher in weanling SHR (15.2 ± 2.0, 37 ± 4.2) than in WKY. PRA measured in samples collected from a separate group of unanesthetized weanling SHR was also greater than in age-matched WKY. In adult SHR, PRA (6.1 ± 0.9) and plasma aldosterone (20.0 ± 2.7) were decreased. During the weanling period Na+-K+-ATPase activity in SHR was not only greater than in age-matched WKY but was also increased compared to adult normotensive and hypertensive rats (137 ± 9 weanling SHR, 89 ± 7 weanling WKY, 73 ± 11 adult SHR, 84 ± 17 adult WKY). Thus, during the weanling period the renin-angiotensin-aldosterone (R-A-A) system and renal Na+-K+-ATPase activity are activated in SHR. The elevation of Na+-K+-ATPase activity may be due to increased aldosterone levels. It was noted, however, that plasma aldosterone was similar in adult WKY and weanling SHR, while Na+-K+-ATPase activity was higher in SHR. These findings involving R-A-A and renal Na+-K+-ATPase activity prior to the elevation of blood pressure suggest that the kidneys may play a role in the initiation of hypertension in SHR.

Penbutolol: A New Beta Blocker in the Treatment of Moderate Essential Hypertension

T a value of beta-receptor antagonism in the treatment of hypertension is now well recognized. Propranolol was the first beta-adrenergic blocking agent to be approved in the United States for the treatment of hypertension. Since its introduction, a wide variety of beta-receptor antagonists that are less toxic and more long-lasting in their action have found use in the treatment of hypertension. Among these are alp renolol, pindolol, timolol, atenolol, sotalol, acebutolol, and oxprenolol. Recently, another nonselective betaadrenergic blocking agent, penbutolol

Circadian Rhythms of Plasma Renin Levels in the Anesthetized Rat

Circadian rhythms of plasma renin activity (PRA) is described in the ether anesthetized rat. PRA values are significantly higher than corresponding values previously reported in the awake rat. Peak activity was observed at 12.00 and 16.00 h, similar to the pattern of diurnal rhythm established in the conscious rat. The reproducibility of PRA in the anesthetized rat is demonstrated by relatively constant values obtained from a separate group of rats bled at the same hour every other week. In addition, each sample was also incubated with excess renin substrate for the determination of relative plasma renin concentration (PRC). The pattern obtained for PRC is similar to that of PRA, indicating that the circadian rhythms result from variations of plasma renin rather than changes in renin substrate. Furthermore, although ether anesthesia raises the basal levels of PRA, it does not interfere with the demonstration of the normal pattern of circadian rhythms.

A new model of genetic hypertension in rats with superficial glomeruli.

Despite renal involvement in the genesis of hypertension, the precise renal hemodynamic events prior to and during development of hypertension have not been obtainable by direct study in the available rat models of genetic hypertension. We have developed a model of genetic salt-sensitive hypertension in rats with superficial glomeruli, using the protocol described by Dahl to develop the Brookhaven model. Adult Munich Wistar rats were purchased from Charles River and bred in our laboratory. Offspring were allowed to mature without intervention. Systolic blood pressure and body weight were measured weekly to determine the normal longitudinal changes with increasing age for this strain. Balance studies were also carried out longitudinally, and during these studies plasma renin activity (PRA) was determined. When the rats were 16 weeks old, the availability of superficial glomeruli was assessed under microscopic examination and only those rats with numerous superficial glomeruli/field were mated: The offspring of these breeders were used as the zero generation (F0) of salt-sensitive rats, and were treated as described by Dahl. Systolic blood pressure, body weights and balance studies were carried out in this and in all subsequent generations. Sibling breeding was maintained and rats were bred for salt-sensitivity (systolic blood pressure greater than 155 mmHg at the age of 2 months) and availability of superficial glomeruli. Those rats with systolic blood pressure of less than 120 mmHg were bred in an attempt to develop a salt-resistant strain, and untreated Munich Wistar rats were bred to provide another control. Among the salt-sensitive rats, by F4 all had systolic blood pressure greater than 170 mmHg, and reduction of dietary sodium intake in adult hypertensive rats had no effect on systolic blood pressure. Plasma renin activity was low in these rats compared to age-matched Munich Wistar rats, regardless of the level of sodium intake. The strain has progressed to F8.

High vanadate interferes with the Fiske-Subbarow determination of inorganic phosphate.

We evaluated the possibility that oxyions of vanadium might react with molybdate and, in that manner, interfere with the Fiske-Subbarow colorimetric determination of inorganic phosphate. Phosphate (P i) standard curves were prepared (0.03-0.30 μmole/ml) in the presence and absence of oxyvanadium solutions (2 × 10-4 M) prepared from ortho- and metavanadate. Molybdate prepared in 5 N sulfuric acid was added to each standard. Upon addition of a reducing agent to develop color of the phosphomolybdate complex, a less intense color was observed at any given P i concentration in the presence of oxyvanadium species. The slope of the regression line for the P i standard curve in the presence of 2 × 10-4 M oxyvanadium species was markedly depressed. The effect of oxyvanadium was similar when solutions were prepared from ortho- and metavanadate, despite differences in pH of these solutions. In addition, in the final reaction the pH was similar in the presence and absence of oxyvanadium, independent of the source of vanadate used to prepare solutions. Thus, interference by oxyvanadium did not appear to be related to changes in pH of samples containing vanadium oxyions. Interference was concentration dependent and the minimal concentration of vanadium oxyions that interfered was 5 × 10-5 M. The effects of oxyvanadium (2 × 10-4 M) on Mg+2-dependent and Na+-K+-ATPase activities in a renal microsomal preparation were then evaluated through the measurement of inorganic phosphate generation. Enzyme activities were determined with and without correction for interference by oxyvanadium with the method of Fiske and Subbarow. A significant artifactual depression of Mg+2 ATPase activity, but not Na+-K+-ATPase activity, was consistently observed when enzyme activities were not corrected for interference by oxyvanadium with the measurement of inorganic phosphate. These data indicate that when effects of high vanadate concentrations (5 × 10-5 M) on ATP hydrolyzing enzymes are evaluated through changes in P i generation, artifactual depression of enzyme activity may occur.

A simple spectrophotometric determination of submicromolar quantities of vanadium oxyions

Widespread interest has developed in the study of vanadium as an essential nutrient [l] and as a possible regulator of several ATP hydrolysing enzymes [2-41 in mammalian species. Available methods for the determination of vanadium are costly [l, 5, 61, complex [7-121, and of very low sensitivity [13, 141. Oxyvanadium species are known to react with molybdic acid in the presence of phosphate to form a heteropolymolybdate complex [ 15, 161. The complex, molybdivanadophosphoric acid, is characterized by a yellow colour that maximally absorbs light at 385 nm. The intensity of colour resulting from the formation of this heteropoly complex has been shown to vary with changes in the concentration of inorganic phosphate. The dependence of the reaction on the concentration of vanadium oxyions has not been evaluated. In the present study we examined the possibility that the intensity of yellow colour development resulting from the reaction of oxyvanadium with molybdic acid and phosphate may vary as a function of oxyvanadium concentration. The effect of phosphate ions and the pH of the medium on the colour intensity were also investigated. The study included the stoichiometric determination of the composition of the complex species. Experimental

Hypertension in the elderly: pathophysiology and its implications for treatment

Publisher Summary This chapter describes the pathophysiological characteristics of the aging process as related to hypertension. The aging process diminishes aortic wall compliance, widening the pulse pressure and producing a rise in pressure for a given change in volume. Loss of the aortic capacity of maintaining a small pressure difference may result in isolated systolic hypertension, particularly in the aged. In addition, arterial wall rigidity blunts the responsiveness of the aortic and carotid sinus baroreceptors to changes in blood pressure. The insensitivity of baroreceptors impairs cardiac acceleration during hypotension and cardiac slowing in response to acute increases in blood pressure. Safety, convenience, and simplicity are important characteristics of the therapeutic regimen. One must be certain that the patient understands and accepts the rationale of treatment. In addition, non-pharmacologic intervention is a well-accepted measure of reducing blood pressure and may even be used as the sole treatment of blood pressure control in patients with mild hypertension. Measures include weight reduction, lowering of dietary sodium intake, decreased alcohol consumption, exercise, and behavior modification.