Effects of ACE inhibition and beta-blockade on plasminogen activator inhibitor-1 and transforming growth factor-beta1 in carotid glomus and autonomic ganglia in hypertensive rats.
BACKGROUND
Previous studies have demonstrated a high correlation between arterial hypertension and the development of lesions in the carotid glomus (CG) and autonomic ganglia (AG), characterized by extracellular matrix (ECM) expansion and reduction in the number of AG neurons. Because lowering blood pressure (BP) is the first step in controlling the deleterious effects of arterial hypertension, the objective was to evaluate possible differences between the beta-blocker atenolol (AT) and the angiotensin-converting enzyme (ACE) inhibitor ramipril (RAM) regarding a protective role on CG and AG, as target organs in the spontaneously hypertensive rat (SHR).


METHODS
Male 12-week-old SHR and Wistar-Kyoto rats (WKY) were divided into SHR; SHR-RAM, 1 mg/kg/d; SHR-AT, 100 mg/kg/d; and WKY rats. After 6 months, the animals were sacrificed and CG and AG were processed by hematoxylin and eosin (H&E) and Masson's trichrome and immunohistochemistry (transforming growth factor-beta(1) and plasminogen activator inhibitor-1).


RESULTS
At the end of the experiment, SHR-AT and SHR-RAM showed a similar control in BP compared with SHR. However, SHR-RAM presented a significant reduction in ECM expansion in CG, AG, and autonomic nerves. Moreover, the number of neurons in AG was preserved with AT and even more with RAM, when compared with SHR group. Transforming growth factor-beta(1) and plasminogen activator inhibitor-1 were increased in CG and AG in SHR and in SHR-AT, whereas SHR-RAM showed a similar expression to the WKY group.


CONCLUSIONS
According to these results, RAM but not AT provided a significant protective role against structural changes in CG as well as in AG caused by arterial hypertension in SHR. This effect seems to be independent of BP reduction.
Toblli
Jorge E
JE
Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina. jtoblli@hospitalaleman.com
Grana
Daniel
D
Cao
Gabriel
G
Milei
Jose
J
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002344:Carotid Body / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005725:Ganglia, Autonomic / Q000187:drug effects* / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1; D001262:Atenolol; D017257:Ramipril