Renal Hemodynamics during Development of Hypertension in Young Spontaneously Hypertensive Rats

Abstract

Background/Aims: Cross-transplantation studies between animals with genetic hypertension and normotensive animals indicate a key role of the kidney in development of hypertension, and studies in young spontaneously hypertensive rats (SHR) have shown reduced glomerular filtration rate (GFR) and renal blood flow (RBF) for a short period at the age of 4–6 weeks during blood pressure increase. We tested the hypothesis that a decline in GFR during development of hypertension in SHR might be more pronounced in juxtamedullary cortex than other cortical zones. Methods: By use of the aprotinin method, total and zonal cortical GFR was measured in anaesthetized Wistar-Kyoto (WKY) rats and SHR at the ages of 2, 4, 6, 8 and 10 weeks. RBF was measured by a transit time flowmeter. Results: Body and kidney weights in SHR and WKY were not significantly different in any age group (p >0.05). Mean arterial blood pressure (MAP) was not different at the age of 2 weeks (79 ± 6 mm Hg in SHR and 74 ± 5 mm Hg in WKY, p > 0.05), but was significantly higher in 4-week-old SHR (104 ± 1 mm Hg) compared to 4-week-old WKY (77 ± 3 mm Hg) (p < 0.01). The difference in blood pressure increased with age from 4 to 10 weeks. RBF, total GFR, and outer, middle, and inner cortical GFR increased with age but were not different in SHR and WKY in any age group (p >0.05). Renal vascular resistance was increased from 4 weeks of age in SHR (21.5 ± 1.8), significantly higher than WKY (14.4 ± 0.9 mm Hg·ml^–1·min·g) (p < 0.01) and stayed at higher values in older age groups (p ≤ 0.01). Conclusion: RBF, total and zonal GFR are not significantly different in anaesthetized SHR compared to WKY at ages from 2 to 10 weeks and GFR in juxtamedullary cortex is not decreased in SHR during onset of hypertension. The results from the present study indicate that development of hypertension cannot be explained by a temporary decline in RBF or total or zonal GFR.

Increased expression of ENaC subunits and increased apical targeting of AQP2 in the kidneys of spontaneously hypertensive rats

“…Some studies did not observe an increased blood pressure until 6 wk of age; others (22) found high blood pressure even in the newborn SHR. The gradual increase in blood pressure from 6 wk of age seen in the present study is supported by several studies (11,33).…”

Neurobiology of animal models of attention-deficit hyperactivity disorder

“…Methylphenidate increased endogenous dopamine activation of DRD2 in WKY but did not alter DRD2 function in SHR striatum Sagvolden (2000) Reanalysis of data ADHD-like overactivity, motor impulsiveness, and deficient sustained attention in SHR compared to several rat strains Bull et al (2000) Differential reinforcement of low rate responding in an operant task WKY performed better than SHR and Sprague-Dawley rats when low rates of responding were required but performed poorly compared with the other rat strains in those parts of training that required high response rates Russell (2001) In vitro superfusion Increased glutamate-stimulated release of [ 3 H]norepinephrine from SHR prefrontal cortex slices is antagonized by AMPA antagonist, CNQX Lehohla et al (2001) NMDA-stimulated uptake of 45 Ca 2+ Decreased In vitro 45 Ca 2+ uptake into barrel cortex slices of SHR Fellner and Arendshorst (2002) Cytosolic Ca 2+ measured with fura-2 fluorescence Store-operated calcium entry into vascular smooth muscle cells was greater in SHR than WKY. L-channel calcium entry was greater in SHR Christiansen et al (2002) Blood pressure measurement SHR and WKY have similar body weight. Mean arterial blood pressure was not different at 2 weeks but increased from 4 to 10 weeks of age Ueno et al (2002b) Open-field exploration Methylphenidate (0.01-1 mg/kg, i.p.)…”

Intrarenal Aminopeptidase N Inhibition Restores Defective Angiotensin II Type 2-Mediated Natriuresis in Spontaneously Hypertensive Rats

“…One of the proposed mechanisms of the initiation of hypertension in SHR involves a primary defect in renal sodium (Na + ) excretion2-8. Over time, this defect necessitates an increase in renal perfusion pressure, an adaptation which becomes central to the development and maintenance of hypertension9, 10.…”