Nitric oxide and preglomerular vascular lesions in lyon spontaneously hypertensive rats.
Accumulation of Sudan black-stainable (SB+) lipids is a hallmark of the focal inflammato-proliferative lesions that develop along preglomerular vessels in N G-nitro-L-arginine methyl ester (L-NAME) and angiotensin II hypertensive rats. We extended our findings to genetically hypertensive Lyon (LH) rats aged 14 and 30 weeks and to age-matched normotensive (LN) rats. Vessels were isolated by HCl maceration. Despite high systolic blood pressure (SBP), hypercholesterolaemia, albuminuria and increased interlobular and afferent arteriolar media thickness, SB+ lesions were rarely found in LH rats, regardless of age. To probe nitric oxide as a potential source of vascular protection, 14-week-old LN and LH rats received L-NAME for 10 days (20 mg kg-1 day-1, per os), which increased SBP to 174 +/- 5 and to >200 mmHg, respectively. It induced formation of focal SB+ lesions less frequently in LN than LH rats, in which they affected 39 +/- 7, 44 +/- 5 and 15 +/- 5% of arcuate arterial branches, interlobular arteries and afferent arterioles, respectively. Immunoreactive endothelin-1 was found to accumulate at the level of SB+ lesions. Co-administered with L-NAME, hydralazine (15 mg kg-1 day-1, per os) limited SBP rise to approximately 10 mmHg in both LN and LH rats. As a result, SB+ lesions were rare in LN rats, but were frequent in LH rats. In conclusion, preglomerular SB+ lesions are spontaneously lacking in LH rats. Endogenous nitric oxide production provides protection against vascular barotrauma. Endothelin-1 likely plays an autocrine/paracrine role in vascular lesion formation.
Casellas
D
D
Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France.
Bouriquet
N
N
Artuso
A
A
D000375:Aging / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001391:Azo Compounds; D004396:Coloring Agents; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications*; D007678:Kidney Glomerulus / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009281:Naphthalenes; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000033:anatomy & histology*; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology*
D000959:Antihypertensive Agents; D001391:Azo Compounds; D004396:Coloring Agents; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D006830:Hydralazine; D009569:Nitric Oxide; C016118:Sudan Black B; D019331:NG-Nitroarginine Methyl Ester