Blood pressure lability and glomerulosclerosis after normotensive 5/6 renal mass reduction in the rat.
BACKGROUND
Hypertension plays a major role in the progression of both experimental and clinical chronic renal disease. However, the pathogenesis of the more slowly developing glomerulosclerosis that is seen even in the absence of overt hypertension, both in renal mass reduction models and in humans with chronic renal disease, remains controversial.


METHODS
The relationship of such glomerulosclerosis to the ambient blood pressure profiles was examined in the normotensive approximately 5/6 surgical excision rat remnant kidney model. Blood pressure was radiotelemetrically monitored at 10-minute intervals for 15 to 16 weeks ( approximately 15,000 blood pressure readings) in untreated rats (N= 13), or those treated with enalapril (N= 8), amlodipine (N= 9), or a combination of hydralazine, reserpine, and hydrochlorothiazide (N= 10).


RESULTS
Even in these normotensive rats (systolic blood pressure <140 mm Hg), % glomerulosclerosis was significantly correlated with the overall average systolic blood pressure (r= 0.62, P < 0.0001; N= 40). However, much stronger correlations were observed between glomerulosclerosis and the % systolic blood pressure readings >150 mm Hg (r= 0.77, P < 0.0001) and the standard deviation of the average systolic blood pressure (r= 0.87, P < 0.0001).


CONCLUSIONS
These data indicate that pressure dependent injury mechanisms continue to contribute to glomerular injury even within the "normotensive" blood pressure range in rats with reduced renal mass. This most likely represents the consequence of the impairment of protective renal autoregulation and enhanced glomerular transmission of the blood pressure fluctuations into the hypertensive range characteristic of the conscious state in both experimental animals and in humans. Such pathophysiology supports the need for more aggressive and around-the-clock blood pressure control in chronic renal disease.
Griffin
Karen A
KA
Department of Internal Medicine, Loyola University Medical Center and Hines VA Hospital, Maywood, Illinois 60153, USA. Martha.Prado@med.va.gov
Picken
Maria M
MM
Bidani
Anil K
AK
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology; D005923:Glomerulosclerosis, Focal Segmental / Q000503:physiopathology*; D006830:Hydralazine / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008991:Monitoring, Physiologic; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D013686:Telemetry
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D006830:Hydralazine; D004656:Enalapril; D012110:Reserpine