Table 1.

Pharmacological and non-pharmacological treatments studied in hypertensive/diabetic animal models.

Animal model	Treatment	Main results	Reference
Zucker fatty rats	Pharmacological
	ARB derivativesR-147176	strongly inhibited advanced glycation while less effective than olmesartan in AT1R binding, it minimally lowers blood pressure Significant renoprotection.	Izuhara et al., 2008 [72]
	Nateglinide insulinotropic agent + Telmisartan	Improved glucose metabolism Restored lowered plasma adiponectin levels	Kajioka et al.,2007 [26]
	Losartan	Lowered blood pressure No significant effect on albuminuria, or glomerular or tubulointerstitial injury	Crary et al., 1995 [19]
	Losartan	Improved both early and late survival of large MI Reduced adrenergic stimulation accompanied by fewer ventricular arrhythmias	Pourdjabbar et al., 2005 [21]
	Irbesartan	Preserved renal function and metabolic profile Substantially improved survival	Janiak et al., 2006 [22]
	Olmesartan	Slowed progression of nephropathy in type 2 diabetes without affecting glucose metabolism.	Mizuno et al., 2006 [23]
	Candesartan versus perindopril	Both induced RAS blockade, slowing the progression of glomerulosclerosis, and preserving glomerular cells Both suppressed proteinuria.	Sebekova et al., 2009 [24]
	Losartan and Ramipril; Vasopeptidase inhibitor AVE7688.	Improved diabetic nephropathy by RAS inhibition on several levels, unrelated to its effects on blood pressure and glycemic control, by renal oxidative stress-dependent mechanisms. Reduced renal AGE formation in type 2 diabetes more effectively than the blockade of RAS	Portero-Otín et al., 2008 [32]
	Lovastatin, a cholesterol synthesis inhibitor	Reduced glomerular injury, leaving glomerular area or glomerular macrophage content unchanged	O'Donnell et al., 1993 [29]
	Enalapril + HMG-CoA reductase inhibitor – statin	Attenuated endothelial-dependent responses in coronary vessels of both Zucker Obese and ZDF rats.	Oltman et al., 2008 [31]
	Non- pharmacological
	Various combinations of essential oils	Fenugreek may block glucose absorption Cinnamon may have insulin-like action and affect insulin signaling	Talpur et al.,2005 [34]
	Stevia rebaudianabertoni (SrB)	SrB extracts lowered plasma glucose in diabetics Stevioside + soy protein SPI exhibited preventive action on development of type 2 diabetes	Jeppesen et al., 2006 [46]
	Quercetin, a flavonoid abundant in fruits and vegetables	Reduced blood pressure Prevented morphological and functional changes in heart, vessels and kidney	Perez-Vizcaino et al., 2009 [36]
Goto-Kakizaki rats	Pharmacological
	Omapatrilat and Enalapril	Comparable blood pressure-lowering and renoprotective properties Omapatrilat prevented vascular dysfunction in diabetes more effectively than enalapril	Cheng et al., 2005 [39]
	Non- pharmacological
	Diterpene glycoside stevioside (SVS) and soy bean protein	Combination has positive synergistic effects on components of metabolic syndrome: hypertension, hyperglycemia, dyslipidemia	Jeppesen et al., 2006 [46]
	Lupin and soy protein	Lupin improved endothelium-dependent vasorelaxation	Pilvi et al., 2006 [47]
	Cereal fiber barley	Significantly reduced systolic blood pressure lowered plasma levels of total cholesterol, triacylglycerol, and LDL	Li et al., 2004 [48]
SHR/ND mcr-cp rats	Pharmacological
	TelmisartanAmlodipineMoxonidine, selective I imidazdin receptor agonist	All three significantly lowered blood pressure Only telmisartan improved impaired relaxation in response to acetylcholine and the increased protein expression of endothelium NO synthase in thoracic aortas	Kagota et al., 2007 [62]
	Telmisartan	Prevented impaired vasorelaxation Reduced sGC expression Raised nitrotyrosine content in mesenteric arteries	Kagota et al., 2009 [63]
	Caloric restriction Olmesartan NifedipinePioglitazoneCobalt	Caloric restriction corrects metabolic abnormalities and protects kidney without correcting hypertension ARB and CCB lower blood pressure to the same extent, but only ARBs protect the kidney without changes in metabolic abnormalities Proglitazone provides renoprotection unlike insulin Cobalt protects kidney without correcting hypertension and metabolic abnormalities Renoprotection almost always associated with decreased AGE formation	As reviewed in Miyata et al., 2008 [64]; and Miyata & van Ypersele de Strihou, 2009 [85]
	Cobalt	Did not correct hypertension and metabolic abnormalities in hypertensives Reduced proteinuria and histological kidney injury, attributed to up-regulation of HIF and HIF-regulated genes and to alleviation of advanced glycation and oxidative stress	Ohtomo et al., 2008 [66]
	Valsartan	Improved renoprotection at doses higher than required for maximal effect on blood pressure.	Tominaga et al., 2009 [60]
	Hydralazine and Olmesartan	Both agents improved functional and morphologic renal damage, associated with decreased accumulation of AGE in the kidney.	Nangaku et al., 2003 [69]
	Olmesartan (among others) + Hydralazine	Both similarly lowered blood pressure Olmesartan significantly improved all biochemical and molecular parameters related to glomerular and tubulointerstitial damage Hydralazine relieved renal damage but less effectively than olmesartan	Watanabe et al., 2009 [70]
	R-147176 + Olmesartan	R-147176 induced significant renoprotection R-147176 minimally reduced blood pressure R-147176 strongly inhibited advanced glycation R-147176 bound AT1R less effectively than olmesartan	Yasui et al., 2007 [75]
	Non- pharmacological (Natural)
	Fiber-supplemented diet	Prevented abnormalities in the metabolic syndrome much more effectively than an insoluble diet	Yasui et al., 2007 [73]
SHROB rats
	Captopril and S-allylmercaptocapto-pril (CPSSA) = pharmacological and nonpharm-acological approach	Reduced multiple abnormalities of metabolic syndrome. Allylmercaptocaptopril improved glucose tolerance, lowered blood pressure, reduced cardiac hypertrophy, protected against renal disease, and prevented weight gain.	Ernsberger et al., 2007 [58]
CRDH rats	Pharmacological
	Omapatrilat	Beneficial effect on glycemic control	Hofman & Rosenthal, 2004 [78]
	Lercanidipine	Beneficial effect on pathology of myocardium and coronary arteries	Amenta et al., 2003 [79]
	Lercanidipine	Prevented changes in small-sized arteries and glomerular arterioles	Rosenthal et al., 2007 [80]
	Telmisartan and Valsartan	In addition to its hypotensive effect, only telmisartan demonstrated beneficial thiazolidinedione-like effects	Younis et al., in press [82]
	CPSSA	Prevention of weight gain, hypotensive and hypoglycemic	Younis et al., in press [83]