Onset of glomerular hypertension with aging precedes injury in the spontaneously hypertensive rat.
The changes in renal hemodynamics that develop with aging in spontaneously hypertensive rats (SHR) were examined. Micropuncture studies revealed that glomerular capillary pressure was elevated in SHR at 9 mo of age compared with 3-mo-old SHR and 9-mo-old normotensive Wistar-Kyoto rats. Glomerular hypertension developed because of a small increase in systemic blood pressure and a decline in preglomerular vascular resistance, allowing transmission of elevated systemic pressure to the glomerular capillaries. The hemodynamic alterations were not a compensatory response to injury, inasmuch as vascular and glomerular morphology were normal in 9-mo-old SHR. To determine the mechanism of these changes, the activity of several vasoactive systems was examined. Similar changes in renal hemodynamics were observed in young and old SHR after blockade of nitric oxide production and after intravenous administration of endothelin. However, ANG II produced a proportionally greater reduction in glomerular filtration rate than renal blood flow in older SHR. These data suggest that reduced endogenous activity of the renin-angiotensin system leads to glomerular hypertension in aging SHR. Late development of glomerular hypertension may contribute to the subsequent appearance of glomerular sclerosis and progressive renal failure in these rats.
Tolbert
E M
EM
Division of Renal Diseases, Department of Medicine, Brown University School of Medicine, Rhode Island Hospital, Providence, Rhode Island 02903, USA.
Weisstuch
J
J
Feiner
H D
HD
Dworkin
L D
LD
D000375:Aging / Q000473:pathology / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics; D006977:Hypertension, Renal / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011677:Punctures; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester