title: Salt-sensitive hypertension resulting from nitric oxide synthase inhibition is associated with loss of regulation of angiotensin II in the rat.
abstract: In the Dahl salt-sensitive hypertensive rat, a diet containing L-arginine, the natural substrate for nitric oxide synthase, abrogates the hypertension. We postulated that nitric oxide synthase inhibition might induce a salt-sensitive form of hypertension and that this salt sensitivity might be linked to a loss of the regulatory effect of sodium ingestion on angiotensin II (Ang II) and angiotensinogen. Male Wistar-Kyoto rats were randomised to a diet containing 0.008 %, 2.2 % or 4.4 % sodium chloride and to treatment with the NO synthase inhibitor L-NAME (10 mg kg(-1) day(-1)) in the drinking water, or drinking water alone (Controls) for 4 weeks. Blood pressure was measured by tail cuff plethysmography twice weekly. After 4 weeks, the rats were anaesthetised and truncal blood collected for determination of angiotensinogen, renin, angiotensin I (Ang I), Ang II and aldosterone concentrations as well as angiotensin-converting enzyme (ACE) activity. Systolic blood pressure increased with increasing dietary sodium intake in the L-NAME-treated rats (P < 0.05). Plasma renin and aldosterone concentrations decreased with increasing dietary sodium intake in both Control and L-NAME-treated rats. Ang I and ACE activity were unchanged by increasing dietary sodium intake. In contrast, the plasma concentration of Ang II and angiotensinogen increased with increasing dietary sodium (P < 0.05 and P < 0.005, respectively). Treatment with the Ang II receptor blocker, losartan, reversed the blood pressure increase. We conclude that treatment with L-NAME induces an increase in blood pressure that is at least in part salt sensitive. Further, the salt-sensitive component appears to be Ang II-dependent, as it was associated with increasing plasma Ang II levels and could be reversed by treatment with an Ang II receptor antagonist.
authors.affiliation: Hypertension Service, South Western Sydney Area Health Service, The Bankstown-Lidcombe Hospital, Locked Mail Bag 1600, Eldridge Road, Bankstown, NSW 2200, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Hodge
authors.forename: V Z C
authors.initials: VZ
authors.lastname: Ye
authors.forename: K A
authors.initials: KA
authors.lastname: Duggan
mesh_terms: D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood*; D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D017673:Sodium Chloride, Dietary; D000808:Angiotensinogen; D000804:Angiotensin II; D000450:Aldosterone; D000803:Angiotensin I; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester