Telmisartan improves insulin resistance in high renin nonmodulating salt-sensitive hypertensives.
BACKGROUND
Nonmodulating (NMHT) is a high-renin subtype of salt sensitive hypertension, which additionally develops insulin resistance and oxidative stress. Conversely, modulating hypertensives (MHT) normally regulates renal hemodynamics after high sodium intake without metabolic impairment. We postulate that telmisartan, an angiotensin receptor blocker with partial peroxisome proliferators-activated receptorgamma partial agonist, may improve insulin resistance compared with ramipril, an angiotensin-converting enzyme inhibitor (ACEI) in NMHT.


METHODS
We studied 18 NMTH (32 +/- 5y nine men, BMI 29 +/- 3 kg/m2) and 16 MHT (34 +/- 4, 10 men, BMI 28 +/- 5 kg/m2) before and after the crossover administration of ramipril 10 mg (3 months) or telmisartan 80 mg (3 months). In each patient studied we measured, before and after each treatment period, office blood pressure, glycemia and insulinemia before and 60 and 120 min after a glucose overload (75 g), total cholesterol, high-density lipoprotein and low-density lipoprotein fractions, triglycerides and highly sensitive C-protein-reactive protein. After that, HOMA-IR Index was calculated.


RESULTS
Plasma renin activity was higher in NMHT 4.4 +/- 0.5 than MHT 2.6 +/- 0.9 ng.ml.h; P < 0.01. Blood pressure was similarly reduced either in MHT or NMHT by ramipril (MHT: from 159 +/- 10/102 +/- 4 to 142 +/- 6/93 +/- 3 mmHg, P < 0.05; NMHT: from 162 +/- 12/97 +/- 4 to 139 +/- 7/89 +/- 2 mmHg, P < 0.05) or telmisartan (MHT: from 154 +/- 8/96 +/- 5 to 137 +/- 6/88 +/- 4 mmHg, P < 0.05; NMHT: from 161 +/- 9/96 +/- 5 to 137 +/- 5/86 +/- 3 mmHg, P < 0.05). In NMHT, fasting glycemia (99 +/- 10 mg%) and insulinemia (16 +/- 4 microU%) and 120 min glycemia (110 +/- 2 mg%) and insulinemia (57 +/- 9 microU%) were higher than in MHT (fasting: 92 +/- 8 mg% and 9.2 +/- 2 mU%; 120 min: 95 +/- 5 and 21 +/- 5 microU%, P < 0.05). In MHT, after 3 months treatment with either ramipril or telmisartan no changes were found in fasting and 120 min glycemia and insulinemia. In NMHT, telmisartan, after 3 months treatment, significantly reduced fasting and 120 min insulinemia (fasting: 8.4 +/- 2, 120 min: 25 +/- 10 microU%; P < 0.01) compared either to basal values or ramipril treatment. Similarly, only in NMHT, compared with basal values and ramipril treatment, telmisartan improved the HOMA-IR index in both MHT (2.76 +/- 0.16 to 2.24 +/- 0.18, P < 0.05) and NMHT (from: 4.4 +/- 1 to 2.3 +/- 0.7) and triglyceride plasma levels (MHT: from 139 +/- 1.85 to 122 +/- 2.4 mg%, P < 0.05; NMHT: from: 223 +/- 12 to 146 +/- 10 mg%, P < 0.01). Finally, highly sensitive C-protein-reactive protein values were higher in NMHT (0.33 +/- 0.07 mg.dl) than in MHT (0.14 +/- 0.06 mg.dl; P < 0.01). Both treatments reduced highly sensitive C-protein-reactive protein in NMHT. (ramipril from 0.32 +/- 0.05 mg.dl to 0.26 +/- 0.06 m.dl (P < 0.05) and telmisartan from 0.34 +/- 0.05+/- to 0.20 +/- 0.05 mg.dl (P < 0.01).


CONCLUSIONS
Our data suggest that the improvement of the insulin sensitivity by telmisartan, instead of a similar effect on blood pressure shown by both drugs, could be ascribed to the PPAR agonistic action of telmisartan. This opens an interesting therapeutic approach for patients with hypertension and altered glycemic metabolism.
Sanchez
Ramiro A
RA
Hypertension Section and Metabolic Unit, Fundación Favaloro, Buenos Aires, Argentina.
Masnatta
Lucas D
LD
Pesiney
Carolina
C
Fischer
Patricia
P
Ramirez
Agustín José
AJ
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists; D017257:Ramipril / Q000494:pharmacology; D012083:Renin / Q000097:blood*; D055049:Salt Tolerance / Q000502:physiology*; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D008055:Lipids; D047495:PPAR gamma; D002097:C-Reactive Protein; D012083:Renin; D017257:Ramipril; D000077333:Telmisartan