title: Cardiovascular hypertrophy in diabetic spontaneously hypertensive rats: optimizing blockade of the renin-angiotensin system.
abstract: The aim of the present study was to compare the antihypertrophic effects of blockade of the renin-angiotensin system (RAS), vasopeptidase inhibition and calcium channel antagonism on cardiac and vascular hypertrophy in diabetic spontaneously hypertensive rats (SHR). SHR with streptozotocin-induced diabetes were treated with one of the following therapies for 32 weeks: the angiotensin-converting enzyme (ACE) inhibitor captopril (100 mg/kg); the angiotensin AT(1) receptor antagonist valsartan (30 mg/kg); a combination of captopril with valsartan; the vasopeptidase inhibitor mixanpril (100 mg/kg); or the calcium channel antagonist amlodipine (6 mg/kg). Systolic blood pressure and cardiac and mesenteric artery hypertrophy were assessed. Mean systolic blood pressure in diabetic SHR (200+/-5 mmHg) was reduced by captopril (162+/-5 mmHg), valsartan (173+/-5 mmHg), mixanpril (176+/-2 mmHg) and amlodipine (159+/-4 mmHg), and was further reduced by the combination of captopril with valsartan (131+/-5 mmHg). Captopril, valsartan and mixanpril reduced heart and left ventricle weights by approx. 10%. The combination of captopril and valsartan further reduced heart weight (-24%) and left ventricular weight (-29%). Amlodipine did not affect cardiac hypertrophy. Only mixanpril and the combination of captopril and valsartan significantly reduced mesenteric weight. The mesenteric wall/lumen ratio was reduced by all drugs, and to a greater extent by the combination of captopril and valsartan. We conclude that optimizing the blockade of vasoconstrictive pathways such as the RAS, particularly with the combination of ACE inhibition and AT(1) receptor antagonism, is associated with antitrophic effects in the context of diabetes and hypertension. In contrast, calcium channel blockade, despite similar effects on blood pressure, confers less antitrophic effects in the diabetic heart and blood vessels.
authors.affiliation: Baker Heart Research Institute, P.O. Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia.
authors.forename: Markus
authors.initials: M
authors.lastname: Lassila
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Davis
authors.forename: Terri J
authors.initials: TJ
authors.lastname: Allen
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burrell
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Zemin
authors.initials: Z
authors.lastname: Cao
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000638:Amiodarone / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002216:Captopril / Q000627:therapeutic use; D006332:Cardiomegaly / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D006984:Hypertrophy; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology; D015260:Neprilysin / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C086991:mixanpril; D000068756:Valsartan; D002216:Captopril; D012083:Renin; D015260:Neprilysin; D014633:Valine; D000638:Amiodarone; D000409:Alanine