The effect of treatment on the vascular deterioration associated with hypertension, with particular emphasis on renal function

858

382

Micropuncture and morphologic studies were performed in four groups of male Munich-Wistar rats after removal of the right kidney and segmental infarction of two-thirds of the left kidney. Groups 1 and 3 received no specific therapy. Groups 2 and 4 were treated with the angiotensin I converting enzyme inhibitor, enalapril, 50 mg/liter of which was put in their drinking water. All rats were fed standard chow. Groups 1 and 2 underwent micropuncture study 4 wk after renal ablation. Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR) due to high average values for the mean glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 rats, treatment with enalapril prevented systemic hypertension and maintained the mean glomerular transcapillary hydraulic pressure gradient at nearnormal levels without significantly compromising SNGFR and the glomerular capillary plasma flow rate, as compared with untreated group 1 rats. Groups 3 and 4 were studied 8 wk after renal ablation. Untreated group 3 rats demonstrated persistent systemic hypertension, progressive proteinuria, and glomerular structural lesions, including mesangial expansion and segmental sclerosis. In group 4 rats, treatment with enalapril maintained systemic blood pressure at normal levels over the 8-wk period and significantly limited the development of proteinuria and glomerular lesions. These studies suggest that control of glomerular hypertension effectively limits glomerular injury in rats with renal ablation, and further support the view that glomerular hemodynamic changes mediate progressive renal injury when nephron number is reduced.

Section: Discussionmentioning

confidence: 99%

Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass.

Anderson¹,

Meyer²,

Rennke³

et al. 1985

858

382

“…It has also been observed that uncontrolled systemic arterial hypertension complicating chronic renal insufficiency may hasten this progression to uremia (56). Furthermore, therapy with antihypertensive agents has been reported to stabilize renal function at existing levels in some hypertensive patients with mild to moderate renal dysfunction (57).…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension.

Dworkin¹,

Hostetter²,

Rennke³

et al. 1984

257

102

were not different than group 3 but significantly lower than group 4. QA and SNGFR were lower in group 5 (low protein) than in groups 3 and 4. Furthermore, proteinuria and glomerular structural lesions were abolished in group 5. Morphologic studies performed in groups 6 and 7 showed that early DOC-SALT lesions progress to focal glomerular sclerosis. These studies suggest that continued elevations in glomerular capillary flows and pressures predispose to glomerular injury in this model of systemic arterial hypertension.

“…In patients with chronic renal insufficiency, it has been suggested that uncontrolled systemic hypertension may hasten the progression to uremia (50). It has also been suggested that therapy with antihypertensive agents may retard the rate of functional decline in some patients with mild-to-moderate renal dysfunction (51), or with diabetes mellitus, nephropathy, and hypertension (52,53).…”

Section: Methodsmentioning

confidence: 99%

Glomerular injury in uninephrectomized spontaneously hypertensive rats. A consequence of glomerular capillary hypertension.

Dworkin¹,

Feiner²

1986

185

Micropuncture and/or morphologic studies were performed in intact Wistar-Kyoto rats (WKY) (group 0) intact spontaneously hypertensive rats (SHR) (groups 1 and 5), uninephrectomized (UNX) WKY (groups 2 and 6), and UNX SHR (groups 3 and 4, 7 and 8). UNX was performed when rats were 5 wk of age. Groups 0-4 were observed for 34 wk after which whole kidney clearance and morphologic studies were performed. Groups 5-8 underwent micropuncture study at 10 wk of age. Groups 4 and 8 were fed a diet containing 6% protein. All other rats ingested standard laboratory diet. 5 wk after UNX, normotensive group 6 had higher single nephron glomerular filtration rate (SNGFR) and initial glomerular plasma flow rate (QA) than intact, hypertensive group 5. Glomerular transcapillary hydraulic pressure difference (AP) was similar in these two groups. Hypertensive group 7 exhibited less elevation in SNGFR and QA than group 6, but AP was significantly increased. The presence of glomerular capillary hypertension in UNX SHR at 10 wk was associated with the development of significant proteinuria and an increased incidence of mesangial expansion and glomerular sclerosis at 7 mo (group 3) as compared with groups 0, 1, and 2. Protein restriction prevented the development of increased AP in UNX SHR (group 8) and also conferred long-term protection from increased urinary protein excretion and glomerular injury (group 4). These studies suggest that glomerular capillary hypertension predisposes to glomerular injury in this model of hypertension with reduced renal mass.