Are vasopressin peripheral V1 receptors involved in the development of malignant hypertension and stroke in SHR-SPs?
The aim of this study was to determine whether activation of vasopressin (AVP) peripheral V1 receptors is involved in the development of malignant hypertension, stroke, and end-organ damage in stroke-prone spontaneously hypertensive rats (SHR-SPs). For this purpose, young salt-loaded SHR-SPs were treated orally daily from their 5th to 34th week of age, by a selective AVP V1 receptor antagonist, SR 49059, used in a dose (30 mg/kg) that achieved complete peripheral V1 receptor blockade. Untreated SHR-SPs served as controls. SR 49059 slightly and transiently (8th to 10th week of age) limited the rise in blood pressure, but thereafter systolic blood pressure values were similar in the two groups of SHR-SPs. Stroke-related mortality was not significantly different in SR 49059-treated and in control animals (65% vs 65% at 30 weeks, 65% vs 83% at 34 weeks). SR 49059 did not prevent the increases in fluid intake, diuresis and proteinuria seen in controls. Histological examination of the brain, kidneys and heart revealed that the development of fibrinoid necrosis and arterial thickening was not prevented by SR 49059, nor was that of malignant nephroangiosclerosis and of myocardial infarction and fibrosis. These data strongly suggest that AVP peripheral V1 receptor activation is not involved in the pathological processes that develop in SHR-SPs.
Vacher
E
E
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Richer
C
C
Cazaubon
C
C
Fornes
P
P
Nisato
D
D
Giudicelli
J F
JF
D000367:Age Factors; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D006974:Hypertension, Malignant / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017483:Receptors, Vasopressin / Q000502:physiology*
D017483:Receptors, Vasopressin