Acute depletion of heme by succinylacetone alters vascular responses but does not induce hypertension.

Abstract:

:Heme plays a critical role in blood pressure regulation because it is required by a number of enzymes that synthesize vascular modulators, including nitric oxide (NO), carbon monoxide (CO), guanosine 3',5'-cyclic monophosphate (cGMP), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin. The goal of this study was to examine the vascular effects of a short-term depletion of heme achieved through administration of the heme-synthesis inhibitor succinylacetone (SA), an irreversible inhibitor of aminolevulinic acid dehydratase (ALAD). Rats were depleted of heme by using a 4-day treatment with SA. This treatment impacted hemoenzyme function, decreasing renal nitric oxide synthase (NOS) activity (as indicated by decreased in vitro NOS activity), and increasing kidney microsomal heme oxygenase (HO) activity by 27%. SA treatment also resulted in enhanced reduction in blood pressure after infusions of exogenous NO donor MAHMA NONOate (at high dose) and acetylcholine (at low doses). Nevertheless, this SA treatment was insufficient to produce an overt elevation of basal arterial pressure. This latter lack of effect may be the result of multiple compensatory mechanisms for the regulation of blood pressure.

authors

Soong J,Adams MA,Nakatsu K

doi

10.1139/y08-064

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

613-9

issue

9

eissn

0008-4212

issn

1205-7541

pii

y08-064

journal_volume

86

pub_type

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