Relation of plasma renin to end organ damage and to protection of K+ feeding in stroke-prone hypertensive rats.

Abstract

We studied the effects of regular diet (035% NaCl/1.1% potassium), high sodium diet (4% NaCl/0.75% potassium), or high sodium and high potassium diet (4% NaQ/2.11% potassium) on blood pressure, plasma renin activity, renal and cerebrovascular lesions, and incidence of stroke and mortality in male stroke-prone spontaneously hypertensive rats (SHRSP). In the first 4 weeks, the rise in blood pressure was higher hi high NaQ than in high NaCI/high potassium or regular diet groups. However, by 8 and 12 weeks, the blood pressure in all three groups was similar. After 4 weeks of diet, plasma renin activity was similar in the three groups (3.4±0.8, 4.1±0.9, and 52±1.6 ng/ml/hr, in high NaO, high NaCI/high potassium, and regular diet groups, respectively) and were not related to sodium excretion. After 8 weeks, plasma renin activity was significantly increased only in the high NaQ group (13.7±3.7 ng/ml/hr), and by 12 weeks plasma renin activity was significantly higher in the high NaCl group (253 ±3.6 ng/ml/hr) than in the high NaCI/high potassium (11.1±2.9 ng/ml/hr) or in the regular diet (7.8±4.6 ng/ml/hr) groups. Moderate to severe renal vascular lesions were first detected in the high NaQ group by 8 weeks of diet At 12 weeks, renal vascular damage index (RVDI), estimated hlstologically, was significantly higher in the high NaCl group (RVDI=79±14) than hi the high NaCI/high potassium (RVDI=40±ll) and regular diet (RVDI=7.8±4.6) groups. At this time, incidence of stroke was 81% in high NaCl, 24.5% in high NaCI/high potassium, and 7.7% in regular diet groups. Hie data demonstrate that: 1) the increase in mortality, stroke, and renal and cerebrovascular lesions in SHRSP fed a high sodium diet is associated with a paradoxical rise in plasma renin activity; 2) the protective effect of high potassium hi SHRSP fed a high potassium diet is related to a lower blood pressure at 2 -4 weeks and a lower plasma renin activity, but not a lower blood pressure at 8-12 weeks; 3) this rise in plasma renin activity demonstrates that a high potassium diet suppresses or delays a primary or secondary paradoxical rise hi plasma renin activity and thus, angiotensin JJ in the rats fed a high sodium diet This action together with possible direct effects of potassium hi the vasculature contributes to the protective effect on end organ damage and stroke hi SHRSP. {Hypertension 1990;15:318-326)

Differential Modulation of Uncoupling Protein 2 in Kidneys of Stroke-Prone Spontaneously Hypertensive Rats Under High-Salt/Low-Potassium Diet

“…15 In fact, UCP2 gene and protein levels were markedly downregulated only in the SHRsp kidneys. In contrast, SHRsr kidneys showed upregulation of UCP2 gene and maintained normal protein levels under the same diet.…”

Mapping genetic determinants of kidney damage in rat models

“…171 Strain characteristics SHRSP show salt-sensitive spontaneous hypertension, vascular and particularly cerebrovascular lesions associated with a high incidence of strokes. 160,171,173,174 In addition, SHRSP develop salt-induced renal damage such as albuminuria, 48 severe glomerulosclerosis, tubuloinsterstitial fibrosis, inflammation, 48,160 renal vascular lesions, 173 and an increase in the glomerular renin-angiotensin system. 175 Male SHRSP rats are more affected in developing renal lesions compared with females.…”

Association and cosegregation of stroke with impaired endothelium-dependent vasorelaxation in stroke prone, spontaneously hypertensive rats.

“…The occurrence of stroke in this strain has been recognized as a complex, multifactorial phenomenon in which specific ecogenetic interactions play a decisive role: both elevated blood pressure (9) and a specific dietary regimen (10) (the "Japanese" rat chow, which is higher in sodium, and lower in potassium and protein than Western diets) (11) are essential permissive elements to produce the stroke-prone phenotype. If these conditions are met, SHRSP show an extremely high rate of stroke which occurs rapidly within a few weeks to months (12)(13)(14)(15).…”