N(G)-nitro-L-arginine methyl ester-induced hypertension and natriuretic peptide gene expression: inhibition by angiotensin II type 1 receptor antagonism.
This study examined the role of angiotensin II in the increase of blood pressure, activation of cardiac natriuretic peptide gene expression, left ventricular hypertrophy, and vascular changes in nitric oxide-deficient hypertension. N(G)-nitro->L-arginine methyl ester (>L-NAME, 20 mg/kg/d), angiotensin II type 1 receptor (AT ) antagonist losartan (20 mg/kg/d), or their combination were administered orally for 8 weeks in Wistar rats. >L-NAME elevated systolic blood pressure, which reached its maximum within 4 weeks (200 +/- 4 mm Hg). Despite hypertension, >L-NAME administration for 8 weeks did not induce left ventricular hypertrophy. Losartan treatment significantly decreased the development of hypertension induced by >L-NAME and decreased left ventricular hypertrophy in untreated rats. In contrast, losartan did not prevent the hypertrophic remodeling of the mesenteric resistance arteries induced by >L-NAME. >L-NAME treatment increased ventricular atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels and immunoreactive BNP levels significantly. Losartan therapy decreased the >l-NAME-induced ventricular ANP gene expression by 69% (p < 0.05) and also reduced ventricular BNP mRNA levels so that it did not differ from control. Losartan treatment alone decreased ventricular immunoreactive ANP and BNP levels by 30% (p < 0.05). These results show that ventricular ANP and BNP gene expression are dissociated from the increased ventricular mass in nitric oxide deficiency-induced hypertension. Results suggest that >l-NAME-induced hypertension and the associated activation of ventricular ANP and BNP gene expression are, at least in part, mediated by angiotensin II, whereas the resistance vessel hypertrophy following nitric oxide synthase inhibition is angiotensin II independent.
Suo
Maria
M
Department of Pharmacology, University of Oulu, Finland.
Kalliovalkama
Jarkko
J
Pörsti
Ilkka
I
Jolma
Pasi
P
Tolvanen
Jari-Petteri
JP
Vuolteenaho
Olli
O
Ruskoaho
Heikki
H
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester