A comparative study of morphological changes in spontaneously hypertensive rats and normotensive Wistar Kyoto rats treated with an angiotensin-converting enzyme inhibitor or a calcium-channel blocker.
It is not clear whether some pathological changes in hypertension are directly pressure-dependent, or hormonally induced, or both. The aortic arch has apparently never before been studied for those changes. The aim of this study was to compare the effects of controlling angiotensin II (Ang II) and/or blood pressure (BP), directly at the inception of hypertension, on the aortic arch, the left ventricle of the heart (LV), and the kidneys of spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) rats. An angiotensin-converting enzyme inhibitor (ACEI, enalapril) and a calcium-channel blocker (nifedipine) were used for 21 weeks. After treatment, rats were assessed for arterial plasma renin activity (PRA). The LV, aortic arch, and kidneys were then excised for the determination of organ and tissue weight in some of the animals, while in others the aortic arch was fixed in situ and processed for microscopic analysis. Both enalapril and nifedipine levelled BP in the SHRs to almost normal values. Enalapril was able to prevent the increase in LV and kidney weights (p=0.04 wet, p<0.001 dry; p<0.001 wet and dry, respectively) and the increase in the weight of the aortic arch and in the thickness of its media (p<0.001 wet and dry; p<0.001, respectively) seen in untreated SHRs. This was associated with a larger lumen diameter (p<0.001) and a lower media to lumen ratio (p=0.01). In contrast, nifedipine did not prevent any of the changes described. Neither nifedipine nor enalapril treatment had any effects on PRA in either rat strain. Our results support previous observations that BP is not the only factor causing some of the pathological changes in hypertension; tissue Ang II level may also play a major role.
Department of Surgery, Faculty of Medicine, The University of Sydney, Sydney, NSW 2006, Australia. freds@medicine.usyd.edu.au
F H
FH
Saleh
A R
AR
Jurjus
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004656:Enalapril / Q000627:therapeutic use; D006352:Heart Ventricles / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology*; D007668:Kidney / Q000473:pathology; D008297:Male; D009543:Nifedipine / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004656:Enalapril; D012083:Renin; D009543:Nifedipine