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E A Wilczynski

Publications and source records attributed to E A Wilczynski.

11 recordsLinked to original sources
PubMed1992

Dietary sodium restriction and the development of two-kidney, one-clip hypertension in young versus adult rats.

To determine the effects of moderate versus severe dietary sodium restriction on the development of 2-kidney, 1-clip (2K,1C) hypertension, young male Wistar rats were placed on diets containing 9, 26, or 101 (control) mumol sodium/g food. Three days later, a solid silver clip (i.d. 0.20 mm) was placed on the left renal artery and diets were continued up to 6 weeks. Adult rats received a 0.25-mm clip. In young clipped rats receiving the 101 mumol/g diet, blood pressure (BP), plasma renin activity (PRA), and BP response to captopril were increased as early as 1 week after clipping and increased further over time. Moderate sodium restriction (26 mumol sodium/g) led to only a slight delay in the development of hypertension; the levels of BP and PRA, the BP response to captopril, and the extent of cardiac hypertrophy achieved by 6 weeks were not different between the 2K, 1C rats receiving 26 or 101 mumol sodium/g. Sodium restriction to 9 mumol/g decreased rate of growth and completely prevented the rise in BP and in left ventricular weight. At 3 and 6 weeks the severely sodium-restricted rats had significantly higher PRA levels than the 2K, 1C control group. However, the BP response to captopril was attenuated relative to the other hypertensive groups. In adult rats, this level of sodium restriction had a small, but significant effect on body weight, but still prevented the increase in BP and in left ventricular weight. In conclusion, dietary sodium restriction can prevent the development of 2K,1C hypertension in both young and adult rats, but only if the restriction is severe. This effect may relate to a marked reduction in the pressor effectiveness of the renin-angiotensin system by low sodium intake per se or by associated metabolic or other changes.

Aging↗
PubMed1988

Serotonergic mechanisms mediate renal sympathoinhibition during severe hemorrhage in rats.

Hemorrhage in rats produces reflex decreases in heart rate (HR) and renal sympathetic nerve activity (RSNA). Because serotonergic antagonists attenuate hemorrhage-induced vagal-mediated bradycardia, we determined whether blockade of serotonin synthesis by p-chlorophenylalanine (PCPA) or of serotonin receptors with methysergide would also abolish the renal sympathoinhibition. Mean arterial pressure (MAP), HR, and RSNA were recorded in chloralose-anesthetized rats pretreated with PCPA (300 mg.kg-1.day-1 X 3 days ip, n = 12) or vehicle (0.3 ml saline, n = 9). During hemorrhage, where MAP was maintained at 50 mmHg for 8 min, vehicle-treated rats decreased HR by 27 +/- 13 beats/min and RSNA by -55 +/- 7%. In PCPA-treated rats, HR and RSNA did not change. Cervical vagotomy abolished the bradycardia and sympathoinhibition during hemorrhage. After acute administration of methysergide (400 micrograms/kg iv, n = 8) hemorrhage produced increases of RSNA, whereas vehicle (0.5 ml saline, n = 7) preserved the renal sympathoinhibition to hemorrhage in conscious rats. Finally, volume expansion (0.88 ml blood/100 g body wt) produced comparable decreases in RSNA in sinoaortic-denervated rats pretreated with PCPA (n = 11) or vehicle (n = 10) (-58 +/- 9 vs. 47 +/- 7%, respectively). We conclude that serotonergic mechanisms are critically involved in vagal afferent inhibition of RSNA during severe hemorrhage in rats.

Animals↗
PubMed1987

Dietary sodium intake and age in spontaneously hypertensive rats: effects on blood pressure and sympathetic activity.

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were placed on sodium restricted diets (9 and 17 mumol/g) or on a regular sodium diet (101 mumol/g) at 2, 4, 7, or 10 weeks of age, and continued until 16 weeks of age. Severe sodium restriction (9 mumol/g) initiated at 2 or 4 weeks of age prevented hypertension development in SHR and severely retarded growth. Hypertension development was attenuated when 9 mumol/g was initiated at 7 weeks of age, and was not affected when started at 10 weeks of age. Mean arterial pressure (MAP) in WKY receiving 9 mumol Na/g initiated at 2 and 4 weeks of age was below normal, but was not affected when this diet was given at 7 or 10 weeks of age. Less severe sodium restriction (17 mumol Na/g) resulted in a reduction in hypertension development when initiated at 2, 4, and 7 weeks of age, but not at 10 weeks of age. MAP was normal in WKY receiving 17 mumol Na/g at all ages of diet initiation. When the 9 or 17 mumol Na/g diet were initiated at 2, 4, and 7 weeks of age, the response of blood pressure to hexamethonium administration was blunted in SHR relative to both WKY receiving the same diet, and to control SHR receiving 101 mumol Na/g. We conclude that both WKY and SHR require a minimum amount of dietary sodium for normal growth and for the achievement of normal BP in WKY, and hypertension in SHR. This sodium requirement decreases with age. SHR and WKY exhibit similar sensitivities to sodium intake with respect to body weight, but the effects on BP are more pronounced in SHR. The BP lowering effects of dietary sodium restriction may be due to a blunting of the pressor effectiveness of the sympathetic nervous system.

Aging↗
PubMed1987

Prevention of hypertension and maintenance of normotension in spontaneously hypertensive rats is dependent on continuous severe dietary sodium restriction.

Spontaneously hypertensive rats were placed on a very low (9 mumol/g) or control (101 mumol/g) sodium diet at birth or 4 weeks of age. These diets were continued to 16 weeks of age, or at 10 weeks were increased from 9 to 26 or 101 mumol/g. Sodium restriction initiated up to 4 weeks of age and continued to 16 weeks of age severely retarded growth, prevented the development of hypertension, and reduced effective sympathetic activity as assessed by the response of blood pressure to ganglionic blockade. Only a small increase in sodium intake at 10 weeks of age (to 26 mumol/g or more) resulted in a marked increase in growth rate, an elevation of blood pressure, and a return of the response to ganglionic blockade towards normal. These data indicate that very severe sodium restriction must be continuous to maintain decreased sympathetic activity and normal blood pressure in spontaneously hypertensive rats. It appears that severe dietary sodium restriction suppresses one or more of the mechanisms involved in normal growth and development of hypertension in spontaneously hypertensive rats, but these mechanisms may still proceed once the sodium intake is increased.

Aging↗
PubMed1986

Can total prorenin in human plasma be determined by current activation methods?

A proper evaluation of the physiological significance of plasma prorenin depends on its accurate determination. However, current activation methods do not necessarily measure total prorenin, or a known proportion of it, even when carried out to apparent completion. Thus, extending cold activation of human plasma at -4 degrees C generally revealed progressive increments of prorenin, mainly during the first 15 days, but the total and the time required to achieve it varied considerably among individuals. Similarly, the titration curves of individual plasmas varied with increments of added trypsin and achieved totals that were not necessarily greater than those obtained by cold activation. This indicates the inappropriateness of attributing greater effectiveness to one method over the other. When the two methods were paired in sequence, a synergism was apparent in that prorenin estimates increased consistently; in one case more than 10-fold. Thus, total prorenin by any single method generally fell short of the total achieved by double methods. However, this too may still not represent the unknown true total prorenin. The sequence of activation steps was important, providing clues as to the mechanism of the observed synergism. Trypsin-before-cold activation proved to be more effective than trypsin-after-cold activation, with no further advantage being gained from triple treatments involving cold before and after trypsin, or trypsin before and after cold. The inferiority of trypsin-after-cold activation was apparently due to sensitization of the plasma to the destructive effects of trypsin, shifting its titration curve to the left.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Extrarenal prorenin in plasma requires an activator of renal origin.

Plasma prorenin may be of renal or extrarenal origin, and its conversion to renin may be catalyzed by renal or extrarenal enzymes. We tested the effect of bilateral nephrectomy and sham bilateral nephrectomy on plasma renin and prorenin in dogs, using low (3 mg/ml) and high (5 mg/ml) concentrations of trypsin to activate the prorenin. In the nephrectomized dogs, active plasma renin quickly disappeared, whereas plasma prorenin (inactive renin) increased by up to 300% during the first 24 hours after surgery, suggesting that it was released rapidly from a major extrarenal source but not converted to renin in the absence of the kidneys. In the sham surgery (control) group, plasma renin activity increased by up to 400% in the first 24 hours but returned almost to baseline by 48 hours, whereas prorenin remained at the preoperative value or fell below it. The quantity of prorenin varied greatly between the groups according to the time after surgery and the different concentrations of trypsin used. In the nephrectomy group, low and high trypsin levels resulted in similar prorenin values during the first 3 hours, but later on, the high trypsin level resulted in about twice as much prorenin. In the control group, high trypsin levels generally produced lower prorenin values than did low trypsin levels. Since trypsin is believed to interact with endogenous convertase enzymes in converting prorenin, a high requirement for it after bilateral nephrectomy suggests that removal of the kidneys causes a deficiency of such convertases. Conversely, the low requirement for trypsin after the stress of sham surgery suggests enhanced plasma convertase activity in the presence of the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Evidence for beta-adrenergic regulation of renal and extrarenal plasma prorenin and renin in dogs.

Beta blockade with propranolol for 7 days in healthy normotensive dogs produced a sustained 20-25% drop in heart rate, but only a transient suppression of blood pressure. Plasma renin activity and prorenin were also suppressed transiently, suggesting that both are under beta-receptor regulation. Bilateral nephrectomy (2NX) was followed by rapid clearance of renin from the circulation, at a rate that was minimally influenced by beta blockade. In contrast, the plasma prorenin level rose markedly to a peak within an hour after surgery, leveled off during the next 24 hr, dropped almost toward the pre-2NX baseline by 48 hr, but proceeded to rise again between 48 and 120 hr. Propranolol administration before and during the 2NX period reduced the detectable prorenin, suggesting that its extrarenal source is under beta-adrenergic regulation. The rapid increment of prorenin after 2NX suggests that extrarenal prorenin may have constituted part of the total plasma prorenin before 2NX, and/or had developed sufficiently quickly afterwards to replace and exceed the disappearing renal prorenin. Any fresh increment beyond 48 hr could presumably have been only extrarenal. These observations suggest the existence of a rich beta-regulated extrarenal source of prorenin capable of rapidly supplying the plasma. However, no renin-angiotesin was apparently produced from this prorenin in the nephrectomized state, implying the lack of renal "convertase," without which the prorenin convertase mechanism as a whole was rendered ineffective. The source of the extrarenal prorenin and the identity of the renal convertase remain to be established.

Adrenergic beta-Antagonists↗
PubMed1985

Age dependency of the effects of dietary sodium restriction on blood pressure in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) were placed on sodium restricted diets (9 and 17 mumol/g) or on a regular sodium diet (101 mumol/g) at 2, 7 and 10 weeks of age, and continued until 16 weeks of age. Sodium restriction initiated at 2 weeks prevented (9 mumol/g) or attenuated (17 mumol/g) the development of hypertension, and severely retarded growth. When sodium restriction was started at 7 weeks, these effects were not so pronounced. Starting at 10 weeks, sodium restriction no longer affected blood pressure, although growth rate was still reduced. These results indicate that there is a period early in life in SHR during which hypertension development critically depends on a minimum amount of sodium intake.

Aging↗
PubMed1982

Peculiarities of plasma "prorenin" measurements in man, dog, and rat, and their theoretical implications.

In human plasma, trypsin activates "prorenin" within 1 min at 23 degrees C. It is quickly neutralized by endogenous inhibitors, and the subsequent hourly expression of old and new renin activity (PRA) is relatively consistent during 15, 30, or 60 min incubation at 37 degrees. In dog plasma, prorenin activation requires much higher trypsin concentrations - 3-5 mg/ml, vs 0.5-1.5 mg in humans - implying a higher content of endogenous protease inhibitors, and/or the lack of some endogenous mediator of the action of trypsin. These could also be partly responsible for the observed lack of cryoactivation in dogs. The effect of trypsin in dog plasma does not end abruptly as in humans. A post-tryptic prorenin "convertase" continues to act at 37 degrees, steadily increasing the hourly rate of angiotensin generation as the incubation is prolonged. Neither lima bean trypsin inhibitor (LBTI) nor endogenous inhibitors fully inhibit this trypsin-induced convertase. It is transferable to normal plasma, where it raises the PRA. Pepstatin severely inhibits this effect, most probably by inhibiting the new renin, possibly also by inhibiting the convertase itself. Rat plasma appears intermediate between human and dog plasmas in some respects. Trypsin activates prorenin well at 4 mg/ml, when exposed for 30 min at 23 degrees, provided the subsequent PRA incubation stage is kept short, e.g. 10 vs 30 min. This implies a low tolerance to effective concentrations of trypsin, presumably attributable to the nature and/or quantity of endogenous protease inhibitors. The amount of prorenin, as judged by activation, equals that of dogs. However, active renin is distinctly higher in rats, possibly due to the stressful influence of anesthesia and blood collection. This greatly reduces the prorenin: renin ratio in rats relative to dogs, and brings them closer to the human ratio. Clamping off the renal blood vessels while blood is collected, lowers the basal PRA, and raises the prorenin:renin ratio. Thus, prorenin is detectable in all 3 species, but the best methods for activating it are quite different, implying marked differences in the mechanisms involved.

Animals↗
PubMedDate not supplied

Plasma prorenin in humans and dogs. Species differences and further evidence of a systemic activation cascade.

We have studied the dog as a potential model for the human plasma prorenin-renin system. On a regular sodium intake, healthy conscious dogs apparently have a much lower plasma renin activity (PRA) than healthy human volunteers. Cryoactivation of prorenin is virtually absent in dogs, in contrast to that in humans, but becomes more effective after preacidification of the plasma. The concentration of trypsin required for optimal activation of prorenin is 6 to 10 times higher for dog plasma, revealing a prorenin:renin ratio about 10 times greater than in humans. Dialysis of posttryptic plasma decreases the PRA, but it remains 5 times higher than in pretryptic plasma, indicating that activation is not totally dependent on any renin system component that has been rendered dialyzable by trypsin, e.g., substrate converted to tetradecapeptide (TDP). This argues against the view that tryptic activation is attributable to angiotensin production from TDP by the action of cathepsin D, rather than from new renin converted from prorenin. The posttryptic increase in PRA is evident whether plasma incubation is carried out at pH 6.0 or at 7.4, and can be largely blocked by pepstatin, which also implicates a prorenin-renin mechanism rather than TDP-cathepsin. The low PRA in dogs, the negligible cryoactivation and its improvement by preacidification, and the requirement and tolerance of high trypsin concentrations, all point to greater protease inhibition in dog plasma and/or departures from the enzyme(s) responsible for human prorenin activation. Moreover, the tryptic activation of prorenin is not completed quickly as in human plasma, but carries over into the posttryptic stage of angiotensin generation, even in the presence of excess soybean trypsin inhibitor (SBTI), and other potent inhibitors. Such ongoing prorenin activation cannot be attributed only to trypsin itself, nor to kallikrein (both are inhibited by SBTI), but rather to some other enzyme(s) derived by the action of trypsin. This new prorenin convertase activity (possibly renin itself) can be effectively transferred from trypsinized to control dog plasma, in which it greatly accelerates prorenin activation. Thus, contrary to other reports, dog plasma has a high content of activatable prorenin, and with appropriate methodological changes, the dog can be used as an animal model for physiological and biochemical studies of the prorenin-renin system.

Angiotensin II↗