Renal afferent arteriolar structure in the genetically hypertensive (GH) rat and the ability of losartan and enalapril to cause structural remodelling.
OBJECTIVE
This study aimed to compare the structure of renal afferent arterioles in the genetically hypertensive (GH) rat strain with the normotensive (N) control strain in relation to pathogenesis, and to quantify structural remodelling in GH rats after treatment with losartan and enalapril and to relate this to blood pressure (BP) and left ventricular (LV) mass.


METHODS
GH rats were given losartan 15 mg/kg/day, enalapril 10 mg/kg/day (enalapril 10) or 3 mg/kg/day (enalapril 3) from the age of 4 to 10 weeks. Untreated GH and N groups served as controls. Tail-cuff systolic BP was measured weekly from 4 weeks. At the age of 10 weeks, kidneys were perfused with microspheres to identify afferent arterioles, kidney pieces were fixed, embedded in Technovit and stained sections analysed. Lumen and media plus lumen diameters were measured; media width, media cross-sectional area (CSA) and media/lumen (M/L) ratio were derived.


RESULTS
BP and LV mass were elevated in GH compared with N rats, and reduced by losartan and enalapril 10 and to a lesser degree by enalapril 3. In afferent arterioles, lumen diameter, media width and CSA were smaller in GH than N and M/L ratio was larger. Losartan and enalapril 10 reduced media width and increased lumen diameter, while enalapril 3 increased CSA (in distal arterioles) and lumen diameter. M/L ratio was reduced by losartan and enalapril.


CONCLUSIONS
Abnormal structure of the afferent arteriole, resulting in an increased M/L ratio, could explain abnormalities of renal blood flow and vascular resistance in GH and contribute to the hypertension. In GH, losartan and enalapril reduce BP and LV mass, cause remodelling of afferent arterioles, and lower the M/L ratio to below N levels.
Ledingham
J M
JM
Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
Laverty
R
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects* / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D007668:Kidney / Q000098:blood supply*; D019808:Losartan / Q000494:pharmacology*; D051381:Rats; D012079:Renal Circulation; D014655:Vascular Resistance
D000959:Antihypertensive Agents; D004656:Enalapril; D019808:Losartan