Jorge Areas

Effects of excess sucrose ingestion on the life span of hypertensive rats (SHR)

Because dietary intake of sucrose may influence life span, we assigned 75 Spontaneously Hypertensive Rats (SHR) to be fed 5 diets, i.e., 15 rats were fed each diet. The control diet (I) derived near equal calories from sucrose, proteins, and fats. Diets II and III derived the majority of calories from sucrose with a decrease in calories from proteins (II) and fats (III) respectively. The last 2 diets were relatively low in sucrose with a higher percentage of calories from proteins (IV) and fats (V) respectively. Rats consuming the diets high in sucrose (II, III) had the shortest mean life span. Differences in renal function did not explain the shortened life span. Blood pressures in SHR ingesting high sucrose (II, III) were significantly higher, and longevity correlated with the mean BP of SHR. At post mortem, the majority of SHR showed enlarged hearts and pleural effusions. We conclude that the diets high in sucrose produced higher blood pressures with earlier congestive heart failure which is, at least in part, responsible for the shortened life span.

Macronutrients in the Diet: A Possible Association with Age-Related Hypertension

Cardiovascular diseases are the most important cause of death in the elderly, accounting for approximately half of all mortality beyond age 65.1 Accordingly, elimination of deaths from cardiovascular causes would prolong life expectancy by more than a decade. The key contributor to cardiovascular disorders among the elderly is hypertension. Hypertension accelerates the physiologic aging process in the circulatory system and thus is responsible for diminishing the quality and quantity of life.

Blood Pressure in Unilaterally Nephrectomized Rabbits: A Correlation with Serum Renotropic Activity

Over 40 years ago, Grollman reported that unilateral nephrectomy (UN) in rabbits precipitated hypertension and suggested that liberation of a pressor substance by an ischemic or damaged kidney could not be causative. Because others were unable to corroborate that UN in rabbits led to increased blood pressure (BP), we followed 7 rabbits after UN and 4 rabbits after a sham operation. At 7-10 days postoperatively, BP increased from the baseline average of 83 to an average of 97 mm Hg in the UN rabbits (p less than 0.01). In contrast, BP did not change significantly after sham operation. Measurements of blood chemistries, serum insulin levels and digoxin-like substances showed no significant changes after UN which would explain the BP rise, but plasma renin activity (PRA) rose from 11.4 to 30.3 ng/ml/h, (p less than 0.05). However, similar elevations occurred in sham-operated rabbits that showed no significant change in BP, i.e. 10.6-26.2 ng/ml/h. Measurement of serum renotropic activity after UN, but not after sham operation, also showed a significant elevation above baseline 97.6% (p less than 0.001). The renotropic activity 7-10 days after UN unlike PRA correlated significantly with the changes in BP (r = 0.87, p less than 0.001). We conclude that BP rises after UN in rabbits, confirming Grollmans findings. The correlative rise in BP and serum renotropic activity may play an important role in the BP elevation after UN.

Effects of Sera from Uninephrectomized Rats on Renal Slices: PAH and TEA Uptake and QO2

We followed the effects of sera from unilaterally nephrectomized (uninephectomized) rats compared to sham-operated rats on 3H-p-aminohippurate (3H-PAH) and 14C-tetraethylammonium (14C-TEA) uptake and oxygen consumption (QO2) in incubating rat kidney slices. These studies were based on the assumption that a circulating renotropic substance might also influence various transport mechanisms. Sera were obtained at various times postoperation; the height of renotropic activity occurs 17-24 h after kidney extirpation. Sera removed 17-24 h postuninephrectomy significantly decreased both 3H-PAH and 14C-TEA uptake in incubating kidney slices. Similar to the inability to show significant renotropic activity after 36 h, sera obtained 48, 96, and 168 h postuninephrectomy had no significant influence on 3H-PAH and 14C-TEA uptake. Addition of sera (10% v/v) generally depressed QO2. However, sera obtained from uninephrectomized rats compared to sera from sham-operated rats had relatively more depressive effects on QO2 in renal tissue after 30 min of incubation (p less than 0.01). No significant differences in QO2 were seen when the uninephrectomized and sham-operated sera were added to the tissue immediately or after 60 min of incubation in the sera. These serum studies on 3H-PAH and 14C-TEA uptake simulate in many respects ones performed previously with serum from spontaneously hypertensive and salt-loaded rats and suggest the presence of a common circulating factor.

In vitro Correlation of Glutamine and Glutamate Renal Ammoniagenesis during Adaptation

Renal slices from 191 rats in various states of acid-base balance were investigated for their ability to produce ammonia from both glutamine and glutamate. Under a variety of conditions, in three different type studies, a significantly similar correlation existed between ammonia adaptation from glutamine and glutamate. This relationship was maintained during acute and chronic acidosis and during alkalotic inhibition of renal ammoniagenesis. We conclude from our findings that ammonia adaptation in rats secondary to acute and chronic acidosis is similar, although incomplete during acute acidosis. Our results further support the hypothesis that the rate of glutamate deamination is a major mechanism for overall renal ammonia adaptation in rats during acid-base changes.

Renal Ammonia Production from the Nitrogens of Glutamine in Intact Acidotic Dogs before and after Bicarbonate Infusions

Renal ammonia is produced from the amide nitrogen of glutamine, approximately 33-50%. The remainder derives from the amino nitrogen of glutamine and other non amide sources, probably the amino nitrogens of other amino acids. We investigated the acute effects of acid-base perturbations on ammonia production from amide and non amide nitrogen sources to determine how they interrelate. Infusions of glutamine were given to some intact dogs to vary the renal load. Following an acute alkali challenge to dogs in metabolic acidosis, ammoniagenesis from the amide nitrogens decreased significantly when the presentation of glutamine to the kidney was normal or relatively low, but changed less or even increased when the glutamine load was relatively high. In contrast, ammonia from the non amide sources consistently decreased during acute alkalotic challenge at any glutamine load-high or low. Since decreased glutamine deamination leading to glutamate accumulation is generally associated with decreased deamidation in dogs with normal plasma glutamine concentrations, we explain the discrepancy of deamidation at high glutamine loads to an unmasking of a separate effect on the glutaminase (phosphate-dependent) pathway by the acute acid-base changes. Accordingly, our results indicate more than one influence from acute acid-base changes in vivo on renal ammonia formation, one stimulatory and other inhibitory. Nevertheless, the influence of glutamate removal predominates over the other effect on the phosphate-dependent glutaminase pathway at physiological concentrations of glutamine in the intact dog.