Prevention of high blood pressure by reducing sympathetic innervation in the spontaneously hypertensive rat.
It has previously been reported that the increase in blood pressure in the spontaneously hypertensive rat (SHR) occurs concurrently with a marked increase in thickness of the arterial wall and an increase in vascular innervation, particularly for the small muscular arteries. The purpose of the present study was to determine whether prevention of the increase in vascular innervation could prevent elevation of blood pressure in the SHR. We found that intraperitoneal injection of a single dose of an antiserum to nerve growth factor (anti-NGF) into young SHRs (postnatal day 19-24) caused a marked reduction in mean blood pressure at age 3-4 months from the raised value of 24.2 +/- 0.5 kPa to 18.9 +/- 0.8 kPa. By comparison, treated Wistar Kyoto rats (WKYs) maintained normal blood pressures. The treatment reduced the amplitude of the intracellularly recorded excitatory junction potential and the NA content of mesenteric arteries in the SHR, leaving the values similar to those of control WKYs. The NA content of these vessels was also reduced in treated WKYs. Importantly, the thickness of the vessel wall, which was greater in the SHR than the WKY, was not significantly altered by anti-NGF treatment. It is concluded that anti-NGF treatment during late neonatal development inhibits the increase in the functional levels of vascular innervation observed in the SHR. Furthermore, this increase in the functional levels of vascular innervation is necessary for the development of hypertension in this rat strain.
Brock
J A
JA
Neuroscience Group, Faculty of Medicine and Health Sciences, University of Newcastle, Callaghan, NSW, Australia.
Van Helden
D F
DF
Dosen
P
P
Rush
R A
RA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D004594:Electrophysiology; D006973:Hypertension / Q000503:physiopathology / Q000517:prevention & control*; D008638:Mesenteric Arteries / Q000737:chemistry / Q000294:innervation / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000276:immunology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000378:metabolism
D000906:Antibodies; D009414:Nerve Growth Factors; D014662:Vasoconstrictor Agents; D009638:Norepinephrine