Impaired vasorelaxant responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats.
BACKGROUND
We have previously shown that a locus on rat chromosome 5, termed STR 2, co-localizes with the genes encoding atrial natriuretic and brain natriuretic peptides, and is closely linked to the development of strokes in rats of a F2 hybrid cohort obtained by crossing stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats. We also demonstrated that there are significant differences in vascular functioning that are co-segregated with stroke latency of stroke-prone spontaneously hypertensive rats.


OBJECTIVE
To investigate the vascular responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats.


METHODS
In view of the important vasoactive properties of natriuretic peptides, we tested the vascular responses to 10(-11)-10(-9) mol/l atrial natriuretic peptide and to 10(-11)-10(-7) mol/l brain natriuretic peptide in isolated rings of aortas and internal carotid arteries obtained from stroke-prone and stroke-resistant spontaneously hypertensive rats. The 6-week-old rats were exposed for 4 weeks either to their regular diet (n = 15 of both strains) or to the stroke-permissive Japanese-style diet (n = 14 of both strains). A group of 14 normotensive, age-matched and sex-matched Wistar-Kyoto rats was also studied.


RESULTS
Systolic blood pressures in stroke-prone and stroke-resistant spontaneously hypertensive rats were similar, and were significantly higher than those in Wistar-Kyoto rats. Vascular responses to nitroglycerin, atrial natriuretic peptide, and brain natriuretic peptide in rats of the two hypertensive strains and in Wistar-Kyoto rats fed their regular diet were comparable. In contrast, the vasorelaxant responses to atrial natriuretic peptide in stroke-prone spontaneously hypertensive rats fed Japanese diet were lower both in aortas and in internal carotid arteries than were those in spontaneously hypertensive rats (both P < 0.05 by analysis of variance) and in Wistar-Kyoto rats (both P < 0.05). Similarly, vasorelaxant responses to brain natriuretic peptide were lower both in aortas and in internal carotid arteries of stroke-prone spontaneously hypertensive rats than they were in spontaneously hypertensive rats (both P < 0.05) and in Wistar-Kyoto rats (P < 0.05). The responses to nitroglycerin in the stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats fed Japanese-style diet were also similar.


CONCLUSIONS
The vasorelaxant effects of natriuretic peptides are impaired in stroke-prone spontaneously hypertensive rats. This abnormality could play a role in the pathogenesis of stroke incidence in this hypertensive model.
Russo
R
R
Department of Internal Medicine, Federico II University, Naples, Italy.
Vecchione
C
C
Cosentino
F
F
Natale
A
A
Mele
A F
AF
Muscolo
M
M
Savoia
C
C
Ganten
D
D
Rubattu
S
S
Volpe
M
M
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000502:physiology; D002343:Carotid Artery, Internal / Q000187:drug effects / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D006152:Cyclic GMP / Q000502:physiology; D006973:Hypertension / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000494:pharmacology* / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D005996:Nitroglycerin; D006152:Cyclic GMP