Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat

The fawn-hooded (FH) rat, a strain characterized by a platelet storage-pool disease, developed focal and segmental glomerulosclerosis at the age of 2-3 months (males) and approximately 6 months (females). Male animals died spontaneously at 11-13 months, and females at 15 months of age, both with overt malignant nephrosclerosis. During the first half year of life focal glomeruli showed depositions of IgG, IgA, IgM, C3 and fibrinogen in a segmental pattern and mainly in mesangial areas. Mesangial IgG and IgA were already demonstrable at the age of 5 weeks. On electron microscopy no electron-dense deposits suggestive of immune complexes were found. Mean arterial blood pressure in 5.5-month-old male FH rats was increased compared with that of matched Wistar rats. One-year-old FH rats had severe hypertension. The presumed relationship between the hypertension, the renal lesions and the blood platelet defect is discussed.     

Relationship between blood pressure level,renal histopathological lesions and plasma renin activity in fawn-hooded rats.

The fawn-hooded rat (FH rat) develops hypertension accompanied with focal and segmental glomerulosclerosis and proteinuria, resulting in premature death. In a first experiment the relationship between renal lesions and blood pressure at various ages was investigated. In a second experiment blood pressure was measured weekly from 10 to 38 weeks of age in a number of male FH rats, followed by examination of renal tissues at 40 weeks of age. Plasma renin activity (PRA) had also been determined in individual FH rats. FH rats aged 4.5 weeks had no renal morphological abnormalities. The severity of the glomerulosclerosis increased with age and showed a positive relationship with blood pressure. The scores of the proteinaceous tubular casts also increased with age and they, too, showed a positive correlation with blood pressure. The severity of glomerulosclerosis and proteinaceous casts at 40 weeks of age was related positively to the course of blood pressure throughout life. The final blood pressure level showed a positive correlation with final PRA values. Only FH rats with malignant nephrosclerosis had high PRA values. The renal glomerular and vascular lesions in the FH rat, most likely caused by the hypertension, progressively deteriorate to malignant nephrosclerosis. At that stage PRA values are increased and may be contributing to the development of renal vascular lesions and acceleration of the hypertension.     

Relationship between blood pressure level, renal histopathological lesions and plasma renin activity in fawn-hooded rats

The fawn-hooded rat (FH rat) develops hypertension accompanied with focal and segmental glomerulosclerosis and proteinuria, resulting in premature death. In a first experiment the relationship between renal lesions and blood pressure at various ages was investigated. In a second experiment blood pressure was measured weekly from 10 to 38 weeks of age in a number of male FH rats, followed by examination of renal tissues at 40 weeks of age. Plasma renin activity (PRA) had also been determined in individual FH rats. FH rats aged 4.5 weeks had no renal morphological abnormalities. The severity of the glomerulosclerosis increased with age and showed a positive relationship with blood pressure. The scores of the proteinaceous tubular casts also increased with age and they, too, showed a positive correlation with blood pressure. The severity of glomerulosclerosis and proteinaceous casts at 40 weeks of age was related positively to the course of blood pressure throughout life. The final blood pressure level showed a positive correlation with final PRA values. Only FH rats with malignant nephrosclerosis had high PRA values. The renal glomerular and vascular lesions in the FH rat, most likely caused by the hypertension, progressively deteriorate to malignant nephrosclerosis. At that stage PRA values are increased and may be contributing to the development of renal vascular lesions and acceleration of the hypertension.     

Focal glomerular sclerosis in the fawn-hooded rat.

We have examined the nature of focal glomerular sclerosis (FGS) in fawn-hooded (FH) rats. The fawn-hooded rat develops pathologic features similar to those observed in steroid-resistant focal glomerular sclerosis, ie, by light microscopy some of the glomeruli appear normal but others show areas of solidification confined to one or two lobules of the tuft. The pathogenesis of this disease is not well known and there is a great need for an animal model. In the FH animal, a marked difference in the development of the lesion was noted between male and female rats. Fifty percent of 4-month-old males had proteinuria in excess of 10 mg/day (none of the females had significant proteinuria), while all 12-month-old males had proteinuria in excess of 45 mg/day (female 12-month-old FH rats had mean proteinuria of 7 mg/day). At 6 months of age continuing through 12 months of age, male FH rats had mesangial deposits of IgG, IgM, and, occasionally, C3, demonstrable by immunofluorescence, whether or not FGS was present. Subepithelial electron-dense deposits were never seen by electron microscopy either at 6 of 12 months. Six-month-old animals frequently did not exhibit FGS. Instead, the glomerular epithelial cells, exhibited fusion of foot processes, vacuolization, and, in some areas, focal loss of the epithelial covering on the glomerular basement membrane (GBM). Six-month-old males with proteinuria exhibited focal loss of negative charge from all layers of the filtration barrier. The GBM from sclerotic glomeruli of 12-month-old rats was commonly denuded of epithelium. None of the animals in this study was uremic. FH rats demonstrated FGS associated with progressive glomerular epithelial cell injury.     

Urinary and renal kallikrein in hypertensive fawn-hooded (FH/Wjd) rats

Urinary excretion of kallikrein (UKal), sodium, potassium, protein, and creatinine, as well as the kidney content of kallikrein and renin, was studied in spontaneously hypertensive FH/Wjd (FH) male and female rats and in age- and sex-matched normal Wistar rats. With the exception of 1-month-old rats UKal excretion was significantly lower in FH rats than in Wistar rats. FH females also excreted less UKal than Wistar females. No UKal inhibitor or increased degradation of this enzyme in the urine of FH rats was detected. There was no difference in creatinine clearance, blood urea nitrogen, or serum electrolytes, and calcium between 5-month-old FH and Wistar males. Wistar rat kidneys contained about twice as much kallikrein as FH rat kidneys. From the age of 2 months FH males excreted more sodium, as well as urine, than all other groups. No differences in potassium excretion were observed. Only FH males, 4 months and older, developed proteinuria. FH males and females became hypertensive at the ages of 2 and 4.5 months, respectively. Plasma renin activity, as well as renal renin activity, was significantly lower in FH than in Wistar males. In conclusion, the decrease in UKal activity which precedes the onset of hypertension suggests that the abnormality in the renal kallikrein system may be involved in the pathogenesis of hypertension in FH rats.     

Early immunopathologic events in experimental diabetic nephropathy: A study in dbdb mice

The natural history of the nephropathy in the diabetic mouse ($\text{db}\text{db}$) was examined during the first 5 months of life. Age-matched nondiabetic heterozygotes ($\text{DB}\text{db}$) served as controls. At 1 month of age, diabetic animals were recognized by the appearance of early obesity. Weight gain in the diabetics followed a Gompertz growth curve, which peaked at 4–5 months. Nonfasting blood glucose levels were not significantly different between controls (155 ± 3) and diabetics (169 ± 18) at 1 month, but older diabetics were overtly hyperglycemic. Immunofluorescent microscopy of the diabetic kidney at 1 month showed significant immunoglobulin deposition in the glomerular mesangium as compared to controls. IgM was the most prominent immunoglobin followed by IgG and IgA. Initially focal and segmental, the distribution of fluorescent staining became more diffuse with advancing age, whereas the intensity demonstrated only a modest increase. Diabetics differed significantly from controls at all time periods and with each immunoglobulin stain. Five-month-old diabetics exhibited linear albumin staining on glomerular and tubular basement membranes. Light microscopy revealed focal and segmental mesangial matrix expansion in diabetics at 2 and 3 months, becoming more diffuse in older animals. In this animal model of diabetes mellitus, immunopathologic evidence of glomerulopathy is apparent at the onset of the diabetic state, in the absence of severe hyperglycemia. This observation suggests a subtle alteration in glomerular mesangial function, a factor which may be of importance in the development of progressive glomerulosclerosis.     

Secretory immune responses in ageing rats. I. Immunoglobulin levels.

Immunoglobulin levels in saliva, serum and gastrointestinal perfusates were measured in groups of ageing CDF (F-344)Cr1BR rats. Four age groups were studied, including: (i) weanling (21-35 days), (ii) adult (3-4 months), (iii) midlife (10-12 months), and (iv) senescent (18-20 months). There was no difference in the mean salivary volume and protein levels in the three older groups of rats. Salivary IgA in the weanling rats was significantly lower, having not yet attained adult levels, while salivary IgG was decreased in the senescent group. No IgM was detected in saliva from any of the animals. Serum IgM was elevated in the midlife and senescent rats. In contrast, serum IgG was significantly decreased in the senescent group when compared to the adult or midlife animals. Significant elevations were noted in serum and intestinal perfusate IgA in the senescent rats when compared to the adult group. While salivary IgA from all groups was shown to be greater than 95% polymeric, only the weanling and senescent groups exhibited a tendency toward predominantly polymeric serum IgA (67-70%). The results define altered immunoglobulin profiles in aged rats in both secretory and systemic fluids, which could affect the immunocompetence of these animals.     

Acquired glomerular lesions in patients with Down syndrome

The long-term survival of persons with Down syndrome has dramatically increased over the past 50 years. There are no studies addressing the spectrum of glomerular lesions in these patients. We reviewed the clinical-pathologic characteristics of 17 patients with Down syndrome who underwent renal biopsy. The cohort consisted of 12 whites and 5 African Americans with mean age of 29 years (range, 6-45 years). History of hypothyroidism was present in 8 patients. Renal presentations included renal insufficiency (15 patients, mean serum creatinine 3.4 mg/dL), proteinuria (all patients, including 3 with nephrotic syndrome, mean 24-hour urine protein 4.2 g), and hematuria (14 patients, including 4 with gross hematuria). The glomerular diseases found on biopsy were IgA nephropathy (n = 5 patients), focal segmental glomerulosclerosis (n = 4), membranoproliferative glomerulonephritis (n = 2), acute postinfectious glomerulonephritis (n = 2), pauci-immune crescentic glomerulonephritis (n = 2), membranous glomerulonephritis (n = 1), and lupus nephritis (n = 1). Follow-up (mean, 47 months; range, 2-141 months) was available on 16 patients (94%). Two patients (1 with membranous glomerulonephritis and 1 with acute postinfectious glomerulonephritis) had complete remission; 8 patients (4 with IgA nephropathy, 2 with focal segmental glomerulosclerosis, 1 with lupus nephritis, and 1 with acute postinfectious glomerulonephritis) had chronic kidney disease; and 6 patients (2 with pauci-immune crescentic glomerulonephritis, 2 with membranoproliferative glomerulonephritis, 1 with IgA nephropathy, and 1 with focal segmental glomerulosclerosis) progressed to end-stage renal disease, 4 of whom died. In summary, a wide spectrum of glomerular diseases can be seen in patients with Down syndrome, with IgA nephropathy and focal segmental glomerulosclerosis being the most common. Renal biopsy is necessary to determine the type of glomerular lesion and appropriate treatment.     

Mesangial glomerulonephropathy with deposition of IgG, IgM, and C3 induced by mercuric chloride: a new model.

A mesangial glomerulonephropathy, characterized by the deposition of rat IgG, IgM, and C3 in the glomerular mesangium, was produced in Wistar rats by a prolonged administration of mercuric chloride (HgCl2). The HgCl2 was dissolved in sterile distilled water (0.2 mg. per ml.), and a group of 15 male Wistar rats was given injections subcutaneously three times a week on alternate days at a dosage of 0.15 mg. per 100 gm. of body weight for 27 weeks. A control group of nine rats was given injections of distilled water only. Mesangial glomerulonephropathy developed in 12 of 15 rats injected with HgCl2 and was characterized by the following: (1) coarse granular and nodular deposition of rat IgG, IgM, and C3 in the mesangium of all glomeruli, (2) absence of staining for rat albumin, IgA, and fibrin, (3) presence of electron-dense deposits in the mesangium, (4) focal and segmental proliferation of the mesangial matrix, (5) interstitial inflammation, (6) tubular atrophy, and (7) deposition of periodic acid-Schiff-positive material in the medulla adjacent to the thin limbs of the loops of Henle. Glycosuria and a slight increase in proteinuria were observed transiently in some rats. The blood urea nitrogen levels were normal in all rats. Eluates from the kidneys with heavy mesangial deposits contained rat IgG. However, the eluted antibody failed to react with normal rat kidney tissue components. None of the above findings were present in the control rats. The study provides a model of a mesangial nephropathy that seems to be immunologically induced; however, the mechanism for the formation and deposition of the immune deposits containing rat IgG, IgM, and C3, and the nature of the antigen(s) have not been elucidated.     

Kidney involvement in Behçet's syndrome

Summary The finding of a focal and segmental glomerulonephritis (GN) in a patient with a Behçet's syndrome led us to perform systematic renal biopsies in ten other patients with the disease. Renal biopsy specimens of 11 patients with Behçet's syndrome (followed for 6 months to 15 years) have been studied by light, electron and immunofluorescence microscopy. In all cases, blood pressure and renal function were normal. Proteinuria was present in five patients. By light and electron microscopy, amyloidosis could not be demonstrated in any case. In one patient, the focal and segmental GN was associated with fibrinoid, electron dense, mesangial and irregular subepithelial deposits. These deposits were also detected in seven other patients but to a lesser degree. Arteriolosclerosis was present in all cases. By immuno fluorescence, small scattered granules of C3 were observed in 10 patients in the mesangium and along the capillary basement membrane. They were diffuse in six cases and focal in four. Small focal deposits containing IgA and/or IgG, Clq were also observed in four cases. Circulating immune complexes found in six out of seven patients in whom they were sought. Rare cases of focal and segmental GN and amyloidosis have been reported in Behçet's syndrome. To our knowledge, glomerular C3 deposits have not been yet reported. These findings with the presence of circulating immune complexes suggest that renal symptoms occasionnally observed in Behçet's syndrome could be related to immune complex deposition.     

Patterns of anti-HIV IgG3, IgA and p24Ag in perinatally HIV-1 infected infants

The antibody patterns of HIV-1 IgG3, IgG and IgA and of HIV-1 p24 antigen were investigated in Thai infants born to mothers infected with HIV-1. In the 17 HIV-1 infected infants, anti-HIV antibodies were detected continuously over a period of 15-18 months and a high level of specific IgG3 subclass was observed. Anti-HIV IgA could be detected at 6 months of age whereas p24Ag was detected at 2 months. In 79 uninfected infants, maternal anti-HIV IgG gradually decreased over 9 months whilst specific IgG3 decayed rapidly during the first 6 months. Both p24Ag and anti-HIV IgA were not found in these uninfected infants. Thus, the disappearance of anti-IgG3 subclass antibodies within 6 months can predict whether infants are uninfected whereas the persistence of anti-HIV IgG and IgG3 subclass antibodies, the production of anti-HIV IgA antibody and the presence of p24Ag appear as an adjunct to the diagnosis of HIV vertical transmission. The necessary assays are relatively simple and could be performed individually.     

Massive Empyema Associated With Transient Hypogammaglobulinemia of Infancy and IgA Deficiency

Transient hypogammaglobulinemia of infancy (THI) is originally defined as a physiological maturation defect of immunoglobulin G (IgG) production that occurs at 3-6 months of age and lasts until 18 to 36 months of age. We report here on a 22-month-old child with THI and IgA deficiency, who had massive pneumococcal empyema. Her depressed IgG level returned to normal within 6 months, but IgA level was still low at 6 yr of age. Although THI is an age-dependent and self-limiting disorder, severe infection that includes an atypical presentation of an infection may occur in some patients and this requires evaluation with immunologic study.     

The effect of aging on the secretory immune system of the eye.

The objective of the present study was to examine the influence of aging on the ocular secretory immune system of the eye. Levels of IgA and free secretory component (FSC) were measured in lacrimal glands and/or tears of 0.6, 1.3, 3, 8 and 17-month-old male and female rats. In addition, the FSC output of lacrimal tissue cultured in vitro was evaluated. During the period from 0.6 to 1.3 months of age, the content of tear IgA increased nine- and 13-fold in females and males, respectively. This rise was paralleled by changes in the concentration of tear FSC. Prior to the onset of puberty, FSC could be detected in only 7% of tear samples, whereas after pubertal maturation, tear FSC levels had attained adult concentrations. This tear FSC profile was similar to the age-related pattern of FSC output by lacrimal tissue incubated in vitro. Following puberty, tear IgA content continued to increase in both sexes until adulthood (3 months of age) and then plateaued in females from 8 to 17 months of age. In contrast, tear IgA in males appeared to stabilize from 3 to 8 months and then rose significantly to the highest levels at 17 months of age. This increase in males was also reflected in their lacrimal tissue: IgA content underwent a six-fold elevation from 3 to 17 months. Of interest is that the differential kinetics involved in tear IgA and FSC expression resulted in an age-associated decline in the FSC/IgA ratio from post-puberty to senescence. A striking finding in these studies was the persistence of a sexual dimorphism in the secretory immune system of the eye. After pubertal development, IgA and FSC levels were significantly higher in tears of males, compared to those of females, at all ages tested up to 17 months. These gender- and age-related variations in tear IgA and FSC amounts could not be accounted for by changes in either the volume of, or total protein content in, tears.     

Allergic diseases and asthma in relation to serum immunoglobulins and salivary immunoglobulin A in pre-school children: a follow-up community-based study

BACKGROUND: We have previously reported an association between low IgA and allergic manifestations in early childhood (0-2 years) and have now followed our cohort for an additional 2 years. OBJECTIVE: To evaluate in a longitudinal community-based cohort study the association between maturation of Ig production and allergic manifestations in the first 4 years of life. METHODS: A cohort of 161 randomly selected children was followed from birth to the age of 42-48 months and evaluated at 18-23 months (EV1; n = 179) and again at the age of 42-48 months (EV2; n = 161). Diagnoses were made with the help of a clinical questionnaire, physical examination and skin prick tests (SPTs) to 10 common allergens. Serum immunoglobulins were measured at EV1 and EV2, and salivary IgA (sal-IgA) at EV2. RESULTS: Serum IgA, IgE, IgG1, IgG2 and IgG4 increased from 2 to 4 years of age (P < 0.001) and their levels showed close correlations (P < or = 0.01 for most comparisons). Children with one or more positive SPTs had lower serum IgA (P = 0.004) and IgG4 (P = 0.05) at EV2 than those who did not respond, and children who developed allergic rhinitis between EV1 and EV2 had low sal-IgA (P = 0.006) and IgG3 (P < 0.05) at EV2. Atopic eczema was associated with low sal-IgA at EV2, and children who developed eczema between EV1 and EV2 had significantly lower sal-IgA than those who recovered after EV1 (P = 0.02). CONCLUSION: Allergic manifestations in predisposed children may be influenced by the rate of maturation of immunological components that counteract sensitization or inhibit effector mechanisms of allergy.     

Focal and segmental glomerulosclerosis. Immunohistologic study of 20 renal biopsy specimens

To evaluate the deposition of immunoglobulins and complement and their relationship to sclerotic and nonsclerotic glomerular segments, immunoperoxidase without periodic acid-Schiff counterstain (IMP) and with periodic acid-Schiff counterstain (IMPAS) for IgG, IgA, IgM, and C3 was performed on cryostat-frozen sections using the direct method, along with routine light microscopy and electron microscopy, in a series of 20 renal biopsy specimens from 20 patients with the final diagnosis of focal and segmental glomerulosclerosis. Neither diffuse mesangial nor diffuse glomerular basement membrane deposits were detected by IMP, IMPAS, or electron microscopy. In 18 biopsy specimens, IMPAS demonstrated focal and segmental granular to globular deposits of IgM and/or C3 in sclerotic glomerular segments. In eight biopsy specimens, small granular deposits of IgM and/or C3 deposits were identified in optically normal glomeruli, suggesting that these deposits may precede segmental sclerosis.     

Immunoglobulin levels in white and metis communities in Saskatchewan.

Serum-immunoglobulin levels (IgG, IgM, IgA, IgD, IgE) have been studied in white and metis (Cree Indian) communities in Saskatchewan. The levels of IgG, IgA, IgD and IgE were higher in the metis than in the whites. Both IgG and IgM were higher in females than in males. IgG and IgA levels rose progressively with age. IgM levels rose rapidly during the first year to almost adult levels, and then fell gradually after the age of 30. IgE levels also rose rapidly during the first 3 years of life, were higher on average in children than in adults, and fell to adult levels at puberty. Low levels of IgA were associated with high levels of IgG; they were not associated with either high levels of IgE or an increase in the prevalence of asthma.     

Secretory immune responses in ageing rats. II. Phenotype distribution of lymphocytes in secretory and lymphoid tissues.

The distribution of lymphocyte phenotypes was examined in various tissues from weanling (21-35 days), adult (3-4 months), mid-life (10-12 months) and senescent (18-20 months) rats. Lymphoid tissues included peripheral blood, spleen, cervical, mesenteric and inguinal lymph nodes. Tissues associated with secretory immune responses were also examined, including submandibular and parotid salivary glands, extraorbital lacrimal glands and Peyer's patches. IgA, IgG and IgM B cells were determined by surface Ig staining. Total T cells (W3/13), T helper/inducer (Th) (W3/25), T suppressor/cytotoxic (Ts) (OX8) and immature T cells (Thy 1.1; OX7) were also evaluated. IgG B cells were significantly decreased in lymphoid tissues from the senescent rats, while the weanling group exhibited decreased levels of all three B-cell isotypes compared to adult animals. IgA B cells were significantly decreased in the secretory tissues of the senescent rats, while IgM B cells were increased in both the weanling and senescent groups. Total T-cell percentages were unaffected by ageing in any of the tissues. The only consistent alteration in the lymphoid tissues was a decrease in Thy 1.1-positive cells in the older groups compared to the weanling group. A decreased Th cell percentage was demonstrated in the salivary and lacrimal glands of the weanling and senescent groups. Decreases in Th/Ts ratios, as well as decreased numbers of plasma cell precursors in the secretory tissues of the aged rats, suggests that alterations in normal secretory immune responses may be expected to accompany the ageing process.     

Enumeration of human peripheral blood lymphocytes secreting immunoglobulins of major classes and subclasses in healthy children and adults

The reverse enzyme-linked immunospot assay was modified to enumerate peripheral blood mononuclear cells (PBMC) secreting IgG1–4, IgA1–2, and IgM. Anti-human IgG F(ab')₂ and mouse monoclonal antibodies specific to each of the isotypes were used as solid-phase capture antibodies and developing antibodies, respectively. Although attempts were also made to detect IgD- and IgE-secreting cells (SC), their numbers in the peripheral blood were too few to be reliably estimated. The assay was applied to study healthy subjects including 21 neonates within 3 days of birth, 44 1- to 48-month-old children, and 32 adults. Sixty percent of these neonates had IgM SC in small numbers (<20 per 10⁶ PBMC), but only three neonates had IgSC of other isotypes. In contrast, by 1–2 months of age children had IgSC of all isotypes, including IgA2 and IgG4, often in higher numbers than adults. The relative frequencies of IgSC were IgA1 > IgG1 > IgM > IgG2 > IgG3 > IgG4 > IgA2 in the children and IgA1 > IgG1 > IgA2 > IgM > IgG4 > IgG2 > IgG3 in the adults. The order of the serum concentrations in the adults was IgG1 > IgG2 > IgA > IgM > IgG4 > IgG3. No correlation was found between the serum level and the IgSC number of individual isotypes (except for serum IgA and IgA1-SC). This new methodology should facilitate investigating the current status of immunoglobulin synthesis and the Ig repertoire in adults and children, in health and in disease.Dedicated to the memory of Dr. Charles Reimer.     

Periarteritis nodosa in spontaneously hypertensive rats -- incidence and distribution.

SHR rats (Nihon Rat Inc.) were used to study spontaneous arterial lesions morphologically resembling human periarteritis nodosa (PN). Male SHR rats (159) developed PN in 76.1%, whereas females (39) in 10.3% during a period of 2 to 15 months of age. The frequency of PN in male SHR rats tended to increase with ageing and reached 100% at 9 months of age. PN lesions were widely distributed with only the lungs, brain and aorta being spared. PN in females was restricted to the tongue, parametrium and mesenterium. Male SHR rats with hypertension of more than 180 mm Hg showed PN in 81.7%, whereas in females with the same hypertension PN was found in only 17.4%. Although there was apparent sex difference in the incidence and background of hypertension, male SHR rats might be a useful animal model of human PN.     

PERIARTERITIS NODOSA IN SPONTANEOUSLY HYPERTENSIVE RATS - INCIDENCE AND DISTRIBUTION—

SHR rats (Nihon Rat Inc.) were used to study spontaneous arterial lesions morphologically resembling human periarteritis nodosa (PN). Male SHR rats (159) developed PN in 76.1%, whereas females (39) in 10.3% during a period of 2 to 15 months of age. The frequency of PN in male SHR rats tended to increase with ageing and reached 100% at 9 months of age. PN lesions were widely distributed with only the lungs, brain and aorta being spared. PN in females was restricted to the tongue, parametrium and mesenterium, Male SHR rats with hypertension of more than 180 mm Hg showed PN in 81.7%, whereas in females with the same hypertension PN was found in only 17.4%. Although there was apparent sex difference in the incidence and background of hypertension, male SHR rats might be a useful animal model of human PN.