Renal lesions and proteinuria in the spontaneously hypertensive rat made normotensive by treatment

Abstract

Spontaneously hypertensive rats (SHR) (N = 40) were maintained at normal blood pressure to the age of 100 weeks by treatment (reserpine, hydralazine, and chlorothiazide) beginning at intervals in groups of eight, from the 5th to 45th week. Mortality rates, patterns of proteinuria, and glomerular and arteriolar pathology were compared with that of treated and untreated normotensive Wistar-Kyoto (WKY) controls matched for age (N = 39) and untreated SHR's (N = 26). Treatment clearly prolongs life in SHR's, the mortality rate for untreated being 100% at 75 weeks versus no deaths at that age among 24 SHR's treated before 20th week. At 100 weeks, treated SHR's were excreting eight times the baseline values of urinary protein, whereas WKY's had hardly increased from baseline values. At 100 weeks, normotensive SHR's showed fibrinoid necrosis, sclerosis, and pericapsular fibrosis of glomeruli, whereas no morphologic damage was found in glomeruli or renal arterioles of WKY. Glomerular lesions in normotensive SHR's are indistinguishable in kind from their hypertensive counterparts, but occur somewhat later. Juxtamedullary glomeruli initially suffer the greatest damage and appear to be the major source of urinary protein. These findings speak against the hypothesis of an increased intravascular pressure as the major factor in the pathogenesis of arteriolar sclerosis and rather favor a genetic defect in the vascular system of the SHR, a defect strongly associated with the hypertensive trait. A possible relationship of this defect to inherited membrane abnormalities recently described in RBC and smooth muscle cells of SHR is discussed.

Radical Scavenging Properties of Indapamide and Renal Protection in Dahl Salt-Sensitive Rats.

“…Thus, the discrepancy in the renal protection between indapamide and trichloromethiazide could not be explained by blood pressure reduction alone. A number of studies have reported dissociation of blood pressure reduction from target organ protection (25,26). To explain such discrepancy, much attention has been paid thus far to metabolic changes induced by antihypertensive drugs, e.g.…”

Assessment of the permeability of the blood-retinal barrier in hypertensive rats.

“…2 Spontaneously hypertensive rats (SHR) have been used as an animal model to examine the effects of chronic hypertension. They manifest the characteristic renal lesions of arteriolar nephrosclerosis, 3 and their cerebral blood vessels demonstrate the same increased media thickness and larger vessel to lumen wall ratio found in humans. 4 Although cerebral vessels have been studied extensively in hypertensive humans and in SHR, little is known about the integrity of the BRB either in SHR or after the induction of acute hypertension in normal rats.…”

“…All samples including the plasma samples were prepared for scintillation counting by adding 10 ml of Ready Solv-MP scintillation cocktail (Beckman). 3 H and…”

“…It was necessary to ensure that radioactivity in the retinal sample was not derived from the ciliary body through the vitreous, as the ciliary body has leaky tight junctions and is more permeable to sucrose than is the retina. 3 To eliminate this possibility, the right eye was dissected while frozen to sample the aqueous, anterior vitreous, and posterior vitreous humors so as to estimate the anteriorposterior gradients of radioactivity within the eye to be worked out, as previously described. 6 The retinas, samples of occipital lobe, and all other samples were each put into preweighed scintillation vials, reweighed, and digested overnight at 50°C in 1 ml of M piperidine (Sigma).…”

“…Spontaneously hypertensive rats (SHR) have been used as an animal model to examine the effects of chronic hypertension. They manifest the characteristic renal lesions of arteriolar nephrosclerosis, 3 and their cerebral blood vessels demonstrate the same increased media thickness and larger vessel to lumen wall ratio …”