Manuel Martinez-Maldonado

Retired

Introduction: An endogenous inhibitor of Na,K-ATPase (CTS) is increased in Dahl salt-sensitive (DS) rats and in human cardiovascular pathologies. Hypothesis: Chronic hypertension is a major cause of CTS release which will not be corrected by treatment, and that effectively treated hypertensive patients (HT) will have increased plasma CTS, compared...

The Dahl salt-sensitive rat is a well-established model to study essential hypertension. We first described a subgroup of these rats based on the unique response pattern in systolic blood pressure during the first weeks of exposure to a high salt diet that included cataract formation. We classified this group as cataract-prone Dahl salt-sensitive r...

PAI-1 has been shown to be both profibrotic and antifibrotic in animal models of hepatic fibrosis. Although these models have similarities to human fibrotic liver disease, no rodent model completely recapitulates the clinical situation; indeed, transaminase values in most models of hepatic fibrosis are much higher than in chronic liver diseases in...

Renal aging is not a pathological process since the aging kidney is able to maintain the homeostasis of the internal medium in conditions of health despite the fact that its resources and ability to adapt to challenges of restriction or overload are limited. It should be understood by the reader that we have based the findings in this chapter mostl...

Excess body weight, high blood pressure, and insulin resistance together have been denominated the metabolic syndrome. In this review, we analyze the potential role of angiotensin II (Ang II) and reactive oxygen species in mediating inflammation in the metabolic syndrome. Ang II induces pro-inflammatory genes and other pro-inflammatory substances a...

One of the most visible and contentious issues regarding the fairness of the original system of organ procurement and allocation is the argument that it resulted in great disparities in the total amount of time a patient waited for an organ (i.e. the time from registration at a transplantation center to transplant), depending on where he or she liv...

Hypertension leads to renal disease through a series of mechanisms that seem to be exaggerated in African‐Americans, who have a higher prevalence of both hypertension and end‐stage renal disease than whites. Renal disease itself leads to hypertension, which in turn can contribute to progression of renal disease. Although there are numerous mechanis...

Patients with moderate to severe renal disease have a very high incidence of hypertension. In end-stage renal disease (ESRD) this is true regardless of the nature of the underlying renal disease. Nevertheless, patients with glomerular diseases and autosomal dominant polycystic kidney disease are particularly vulnerable. Evidence is presented that E...

Malnutrition is the most common cause of mortality in the world. It affects underdeveloped as well as industrialized societies, in the latter demonstrating a prevalence in hospitalized patients of between 30 and 50%. Although the prevalence has decreased in recent studies, the problem is still significant among a selected group of patients. The cli...

TUDIES in my laboratory 20 years ago using video time-lapse photography identified for the first time macrophages in cultured glomeruli isolated from animals and patients with crescentic glomerulonephritis. The significance of these findings was later proven by a number of studies in which different macrophage-depletion strategies were shown to inh...

Regardless of the primary etiology of renal disease, the progressive decline in renal function eventually leads to uremia. In most patients with chronic renal insufficiency the signs and symptoms of uremia manifest when glomerular filtration rate (GFR) decreases to less than 15–20mL/min. When GFR reaches a level lower than 5 mL/min, end-stage renal...

Atheroembolic renal disease is an important and often underdiagnosed cause of renal insufficiency in the elderly. Renal damage results from embolization of cholesterol crystals from atherosclerotic plaques in large vessels such as the abdominal aorta to small arteries of the kidney. The typical patient is a white man older than 60 years who has an...

Acute renal failure (ARF) is frequent in aged individuals. In this article, we review the literature and relate our own experience in this field. It is concluded that there are no technical reasons to deny treatment for ARF using any of the available techniques based on age. Attempts to prevent the onset of ARF are important. Prophylaxis may be foc...

: Glucose filtered load (FL), glomerular filtration rate (GFR) and tubular glucose reabsorption (TG) were simultaneously measured in the right, control kidney and in the left kidney with cortical necrosis (CN kidney) in rats with increasing plasma glucose concentrations (PG). Urinary glucose excretion starts when plasma concentrations (threshold va...

Autosomal dominant polycystic kidney disease (ADPKD) is caused by at least two different genes. The ADPKD1 gene is located on chromosome 16p and a second locus is at 4q. Although the ADPKD1 gene is responsible for the majority of the disease in whites, there was no information regarding the gene type in blacks. We studied a black family which prese...

Hypertension is a disorder that, theoretically, is easily detected and effectively treated. Unfortunately, high blood pressure is a painless cardiovascular risk factor that is associated with nonspecific symptomatology and depends—under most circumstances—on life-long treatment for amelioration or control. Paradoxically, these characteristics make...

Unilateral ureteral obstruction (UUO) leads to fibrosis of the obstructed kidney. We tested the hypothesis that interstitial fibrosis in UUO results, at least in part, from enhanced expression of transforming growth factor-beta (TGF-beta) which in turn is regulated by local angiotensin II (Ang II) generation. (The generic name TGF-beta is used to d...

Unilateral ureteral obstruction (UUO) alters the expression of genes encoding for the renin-angiotensin system (RAS). We tested the hypothesis that changes in RAS genes expression occur soon after obstruction. Indeed, measurements during the first 24 hours of UUO showed up-regulation of renin mRNA in the obstructed kidney at 1 hour. UUO also led to...

During the past decade, experimental and clinical evidence has indicated an important role for the renin-angiotensin system in the progressive destruction of nephrons in a wide variety of chronic renal diseases. Studies have indicated that in the subtotally nephrectomized rat model of progressive glomerulosclerosis, in experimental diabetes mellitu...

We have shown that acute (24-hr) unilateral ureteral obstruction (UUO) induces the genes encoding for renin, in juxtaglomerular apparatuses and in tubules, for angiotensin converting enzyme in vascular endothelial cells, and for angiotensinogen in perivascular fat. These molecular changes occur in temporal association to marked reductions in renal...

Pages F660–F669: J. E. Benabe, S. Wang, J. N. Wilcox, and M. Martinez-Maldonado. “Modulation of ANG II receptor and its mRNA in normal rat by low-protein feeding.” Page F662, Table 1: for the third group (NP), the value for renal vascular resistance is incorrect and should be 9± 1 dyn·s·cmx ⁻⁵ ; also for the NP group, the plasma retin activity is i...

Autosomal dominant polycystic kidney disease (ADPKD) is a frequent cause of ESRD, but its frequency in blacks has not been well delineated and its course and the effects of sickle hemoglobin in this disease in blacks have not been previously reported. The occurrence of ADPKD in blacks and whites was determined in two ESRD populations: all ESRD pati...

Pages F660–F669: J. E. Benabe, S. Wang, J. N. Wilcox, and M. Martinez-Maldonado. “Modulation of ANG II receptor and its mRNA in normal rat by low-protein feeding.” Page F662, Table 1: for the third group (NP), the value for renal vascular resistance is incorrect and should be 9 ± 1 dyn·s·cm-5; also for the NP group, the plasma renin activity is inc...

Low-protein feeding results in reduced plasma renin activity (PRA), low prostaglandin production, high intrarenal vascular resistance, and reduced renal plasma flow (RPF) and glomerular filtration rate (GFR) in normal, intact rats. The hemodynamic changes are reversed by converting enzyme inhibitors. In this study, normal rats were fed normal prote...

Renal and systemic hemodynamic responses to an alpha-adrenergic agonist (norepinephrine, NE) and an alpha-adrenergic antagonist (phentolamine, PHEN) were studied in weanling rats pair-fed isocaloric diets containing either normal (NP, 23%) or low (LP, 6%) protein. Mean arterial pressure (MAP) rose less with NE and fell more with PHEN in LP than in...

The effect of 24-hour unilateral ureteral obstruction (UUO) on the expression and regulation of the renin-angiotensin system (RAS) in rats and of pretreatment with lisinopril (5 mg/kg/day) or the AT1-R inhibitor, losartan, (10 mg/kg/day) on renal hemodynamics was evaluated. Both drugs improved the post-obstructed kidney (POK) renal hemodynamics, lo...

Dextrorotatory (+) and levorotatory (-) ozolinone (ozo) were injected directly into the left renal artery of volume-expanded anesthetized dogs. (+)Ozo (40 micrograms/kg/min) had no effect on urine flow and fractional excretion of Na+, Cl-, or K+ when compared with the basal period. Comparison of (-)ozo to (+)ozo revealed the following: urine flow 4...

Low-protein (LP) feeding (6%) of rats results in renal hemodynamic changes that are abolished by converting enzyme and nonpeptide AT1 inhibitors, suggesting a role for intrarenal angiotensin II (ANG II). Dietary protein is a stimulus for the expression of renal renin mRNA in intact and partially nephrectomized rats. In the present study, LP increas...

Congestive heart failure is one of the most important causes of peripheral edema seen in clinical practice. Edema in congestive heart failure is the result of the activation of a series of humoral and neurohumoral mechanisms that promote sodium and water reabsorption by the kidneys and expansion of the extracellular fluid. These mechanisms, in conc...

We report a simple method using copy RNA (cRNA) internal standards for quantitative Northern hybridization. This was accomplished by synthesis of a full-length or "half"-length cRNA and mixing these RNA internal standards with samples to be tested for the abundance of a given mRNA. Both full-length and truncated cRNAs are detected in Northern analy...

The role of antidiuretic hormone (ADH) in the renal concentration defect and hemodynamic changes in protein malnutrition was evaluated in rats with diabetes insipidus (DI) after 2 weeks of low protein feeding. Free water reabsorptive capacity (TcH2O), glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured in the protein deprive...

The mechanism whereby an infusion of amino acids (AA) leads to increments in glomerular filtration rate (GFR) and renal plasma flow (RPF) is incompletely understood. Dopamine (DA) is a catecholamine in which known actions at low doses include the ability to increase both GFR and RPF. Furthermore, urinary DA excretion has been shown to be augmented...

Renovascular hypertension has its experimental counterpart in the two-kidney, one clip model (Goldblatt hypertension). From the study of this model, a general pathophysiological scheme has evolved suggesting that temporal stages in the development and maintenance of hypertension are regulated by complicated hormonal and neural interrelations. The c...

There is a paucity of information about hypertension and its risk factors, prevalence, morbidity, and mortality in many racial minorities in the United States. Most of the population groups discussed in this section are composed of several subgroups that differ culturally, socioeconomically, educationally, and ethnically. This fact, however, does n...

The study of the renal sites and mechanisms of action of diuretics received a major boost by the experiments conducted by the Dallas group in the mid and late sixties [1, 2]. Utilizing clearance techniques and sharp judicious analysis of free water excretion (CH2O) and reabsorption (TcH2O) curves, these investigators set the basis for the present k...

Diuretic therapy may enhance renin release by various mechanisms, principally contraction of extracellular fluid volume and its effects, including a fall in arterial pressure. Awake hydropenic or volume-expanded rats received diuretics (amiloride and hydrochlorothiazide) that are known inhibitors of NaCl transport beyond the macula densa; also the...

Urinary tract obstruction is a frequent cause of acute renal failure that is potentially life threatening but reversible, if it is promptly recognized and corrected. The level of urinary tract obstruction is variable, dependent on the underlying disease, and may range from the loop of Henle to the urethral meatus. Clinical manifestations are most c...

Our earlier studies of cataracts in Dahl salt-sensitive (DS) rats suggested the possibility of altered lens ion transport as a contributing factor in cataractogenesis in this genetic model. We also observed that those weanling DS rats with the greatest pressor response to a high salt diet eventually developed cataracts, and that changes in salt int...

Deoxycorticosterone (DOC) hypertension in the rat is generally induced in rats at an age of approximately 3 months. Both uninephrectomy and a high sodium diet are necessary, however, to induce DOC hypertension. Considering the inability of the developing kidney to adequately excrete a sodium load, we studied the possibility that DOC alone might ind...

Necrosis of the outer two-thirds of the cortex (CN) was induced with boiling water in the left kidney of rats. Two days afterward, morphological damage was shown to be limited to the superficial cortex; deep nephron population was well-preserved. Glucose reabsorption under basal and glucose loading conditions, and extraction of p-aminohippurate, us...

The effects of anaritide, a 25-amino-acid synthetic analogue of ANP, were evaluated in 28 patients with cirrhosis complicated by ascites and/or edema. Each patient received two doses of the agent, as well as an infusion of placebo. Six different doses were tested ranging from 0.015-0.300 [mu]g/kg/min. The infusions lasted for 2 hours and were flank...

We previously described the Dahl salt-sensitive rat as a potential model of cataractogenesis in which cataract formation is associated with hypertension. Cataractous lesions were characterized by a marked lenticular and aqueous humor electrolyte imbalance. In the present study the effects of chronic dietary sodium restriction on cataract formation...

Various studies have shown that a high protein (HP) diet, compared to a low protein (LP) diet, leads to hypercalciuria and alterations in renal and systemic hemodynamics. The authors compared the effects of HP diet to those of normal protein diet (NP) to determine the possible mechanisms by which changes in systemic hemodynamics and hypercalciuria...

The relationship between hyperuricemia, gout, and autosomal dominant polycystic kidney disease (ADPKD) is not widely recognized. In an attempt to further clarify this relationship, the authors have studied 17 patients with ADPKD, 9 controls, 9 patients with proven gout and chronic renal failure, 11 patients with gout and normal renal function, and...

This review will briefly discuss various electrolyte disturbances that occur in patients suffering from cancer. We will highlight those alterations in plasma composition that are directly due to the presence of tumor, indeed, substances produced by tumors may be responsible for the production of various alterations in plasma composition including c...

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 pr...

We have previously reported a high incidence of cataract formation in adult hypertensive salt-sensitive rats, suggesting that hypertension may be an important cataractogenic risk factor. Weanling salt-sensitive rats that eventually developed cataracts showed a marked increase in the pressor response to a high-sodium diet compared to salt-sensitive...

In 1902, Guthrie1 described the unusual occurrence of renal disease in 12 members of a family. In 1927, Alport observed the association of deafness with renal failure in the same family.2 Over the next few decades, the finding of several other families in whom progressive hereditary nephritis coexisted with deafness clearly suggested that this asso...

Weanling and young spontaneously hypertensive rats (SHRs) demonstrate higher plasma renin activity and plasma aldosterone concentration than age-matched normotensive Wistar-Kyoto (WKY) control rats. In addition, this age group exhibits a salt-retaining tendency not seen in WKYs. Nevertheless, when they reach adulthood, these differences between SHR...

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 s...

We assessed the role of angiotensin II in mediating the alterations in renal hemodynamics known to result from low protein feeding to normal rats by examining the effect of the angiotensin-converting enzyme (ACE) inhibitor captopril. 2 wk of low protein (6% casein) diet resulted in decreased glomerular filtration rate (normal protein [NP], 1.82±0.1...

Vanadate is known to inhibit several phosphatases including Na+, K+-ATPase, alkaline phosphatase, and glyceraldehyde-3-P dehydrogenase. Inhibition presumably results because vanadium adopts a stable structure which resembles the transition state of phosphate during the reactions involving these enzymes. We performed experiments to further examine t...

X-band (9.2 GHz) electron spin resonance spectroscopy was used to investigate the binding of vanadyl to calmodulin. Solution spectra, obtained at ambient temperature with various VO2+:calmodulin molar ratios, suggested a binding stoichioimetry of 4 mol of VO2+/mol of protein and the possibility of two classes of binding sites. The latter was confir...

Isosorbide dinitrate was administered sublingually and compared with placebo in a double-blind, randomized fashion to determine its effectiveness and safety in the rapid control of severe arterial hypertension. In 11 patients who received 10 mg of isosorbide dinitrate, blood pressure (BP) dropped from 205 +/- 8/131 +/- 3 to 166 +/- 9/106 +/- 5 mm H...

In previous unrelated studies, we observed a 35 to 50% incidence of cataract formation in several groups of Dahl salt-sensitive hypertensive rats (DS) over a 4-year period. In the present study we evaluated longitudinal changes in blood pressure in DS in which cataracts eventually developed and those in which cataracts did not develop when all anim...

In this cross-cultural study of Puerto Rican and Texas physicians, we have tested the hypothesis that physicians' "humanistic attributes" are culturally related. Differences (P = .05 to .01) were found between mean responses of the two groups of residents to seven of the questions on the Totalitarian-Authoritarian-Dogmatism scale. Factor analysis d...

This chapter reviews the literature until May 1986. The first part covers the anatomic and functional correlates of autosomal dominant polycystic kidney disease (ADPKD) and aspects of renal cell carcinoma that will be of interest to nephrologists. Several other tumors that produce symptomatology that is likely to result in nephrologic consultation,...

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 (Pi) standard curves were prepared (0.03-0.30 mumole/ml) in the presence and absence of oxyvanadium solutions (2 X 10(-4) M) prepared from ortho- and met...

The effect of acute and chronic expansion of the extracellular fluid volume on plasma renin concentration (PRC) was studied in normal Long-Evans rats (LE rats) and in rats with hereditary hypothalamic diabetes insipidus (DI rats). Chronic deoxycorticosterone acetate (DOCA) treatment, combined with a high sodium intake, significantly reduced PRC of...

Protein calorie malnutrition is a world wide problem affecting 30–40% of hospitalized patients in iniultrial societies and hundred of thousands in developing countries.1,2

Vanadate is a well known inhibitor of the Na+, K+-ATPase (1,2). In addition to the effects on the sodium pump, vanadium compounds have been shown to inhibit acid phosphatase, alkaline phosphatase and adenylate kinase (3,4) as well as several of the enzymes in the glycolytic pathway (5), including glyceraldehyde-3-posphate dehydrogenase (6) phosphog...

The response to progressive volume expansion with isotonic saline was studied in sham-operated (CS) rats and in rats with reduced nephron mass after unilateral removal of cortical tissue (CX) or amputation of the kidney poles (NX). Glomerular filtration rate (GFR) in CS kidneys was not statistically different from that in control kidneys. CX and NX...

The interrelationships among plasma renin activity (PRA, ng AI/ml plasma/hr), aldosterone concentration (ng%), and renal Na+-K+-ATPase activity (mumole 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 group...

The inhibition of renin secretion and the vasoconstrictive action of cardiac glycosides may be attributed to increases in cytosolic calcium as a result of inhibition of Na+-K+-ATPase. These studies examined in the dog in vivo the role of calcium on the renal actions of ouabain as assessed from the modifying effects of calcium channel blockers. Sinc...

Intra-arterial infusion of vanadate (VO4) in dogs produces a reduction in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow (V), and the fractional excretion of sodium (FENa+). To evaluate the role of Ca2+ in these changes VO4 was infused into the renal artery in the presence of the calcium antagonists trifluoperazine (TFP), vera...

Vanadate has been recognized as an inhibitor of (Na+, K+)-ATPase (1, 5). Several groups have emphasized it’s potential role as a regulator of the enzyme in the kidney (6), an organ where vanadium tends to accumulate (7). In the dog, intraarterial infusion of vanadate produces a marked vasoconstriction, a decrease in renal blood flow and glomerular...

Ouabain, a specific inhibitor of Na+K+ ATPase, has been shown to inhibit renin release and exert natriuretic and renal vasoconstrictive effects in the dog (1, 2, 3, 4).