Neuropeptide Y in rat sympathetic neurons is altered by genetic hypertension and by age.

Abstract

We have used immunocytochemistry to quantitate neuronai neuropeptide Y in superior cervical ganglia of a strain of nonnotensive Wistar-Otago rats and a related genetically hypertensive strain over the age range 1-60 weeks. The numbers of neuropeptide Y-immunoreactive cells and total ganglionic cell numbers were both greater in ganglia of young nonnotensive than in those of hypertensive rats. Between 10 and 60 weeks of age, peptide immunoreactivity and total cell numbers both fell in nonnotensive rat ganglia but remained constant in ganglia from hypertensive rats. Densitometric analysis showed that the concentrations of neuropeptide Y were similar in neurons of age-matched individuals of both strains, but during aging there was a substantial decline in neuronai peptide content that was similar in both strains and that was not accompanied by any decline in neuronai immunoreactivity for tyrosine hydroxylase. Our results suggest that there is a developmental abnormality of neuropeptide Y in sympathetic neurons of this strain of genetically hypertensive rat and that, furthermore, the aging process is accompanied by a selective loss of neuronai neuropeptide Y that is independent of blood pressure status. (Hypertension 1990;16:63-71) I n adult animals of both the Otago (GH) and the Kyoto (SHR) strains of rat with a hereditary predisposition to hypertension, there is biochemical and functional evidence that peripheral sympathetic activity is inappropriately high.1 -7 Furthermore, neonatal destruction of the peripheral sympathetic nervous system retards the development of hypertension and reduces the absolute extent to which both blood pressure elevation and the associated cardiovascular hypertrophy are seen in adulthood. 8 * 14Also, studies in the GH strain have shown that hypertension can be reversed completely by ganglion blocking agents until the rats are about 4 weeks of age. 15There are, therefore, several lines of evidence to suggest that elevated sympathetic drive may be an etiologic factor in the genesis of high blood pressure in these animal models for essential hypertension. In the sympathetic nervous system, neuropeptide tyrosine or neuropeptide Y (NPY) is jointly localized 23 Therefore, we compared the patterns of NPY immunoreactivity in sympathetic neurons of nonnotensive and GH hypertensive rats from the neonatal period through late adulthood. Methods AnimalsThe rats used in the present study were raised in our animal house from a normotensive white Wistar line originating in the Otago Medical School and from the GH line that was bred from the same stock.24 Breeding was from brother-sister matings, and ah 1 rats were fed a proprietary rat chow (quoted sodium content 0.5%) with water ad libitum. Periodic checks of blood pressures in conscious, prewarmed adult rats using an occlusive tail cuff and a pulse transducer confirmed that resting systolic pressures were less than 140 mm Hg in normotensive rats and at least 170 mm Hg in hypertensive rats.

Modulation of neurotransmitter release by NO is altered in mesenteric arterial bed of spontaneously hypertensive rats

“…Thus the decrease of NO availability in hypertension may also have consequences for the release of NPY and ATP. Alterations in plasma NPY levels have frequently been reported in hypertension models (12,27,44), but the results have been conflicting, possibly because of contamination with plateletderived NPY (29). Responsiveness to ATP and the ATP metabolite adenosine has also been reported to be altered in the SHR (17,21,31).…”

Catecholamine and Neuropeptide Y Levels in Tissues from Young Dahl Rats following 5 Days Low- or High-Salt Diet

“…Previous work from our laboratory [1] using the same age and treatment regimen as the current study showed isolated perfused Adrenal norepinephrine epinephrine 97.8+12.8(6) 411.4 + 51.8" (6) 111.0± 13.1 (7) 470.2 ±60.7" (7) 120.7+18.7 (8) 593.3±69.9 (8) 127.4 ± 17.5 (8) 623.0 + 68.8 (8) Significantly different from DR+ group. b Significantly different from D R-and DR+.…”

“…It is colocalizcd in sympa thetic nerves with norepinephrine, can di rectly cause vasoconstriction and. in the rab bit femoral artery for example, can augment the pressor response to electrical stimulation [6], Hypertensive SHR vasculature shows al terations in content, responsiveness to or developmental pattern of NPY relative to normotensive tissues [7][8][9], A preliminary report of these studies has been made [ 10],…”

Decreased vascular permeability response to substance P in airways of genetically hypertensive rats

“…The overgrowth of SP-containing sensory neurons in the GH is coupled with reduced numbers of sympathetic neurons (Gurusinghe et al, 1990) and both defects are normalized by administration of exogenous NGF in the neonatal period (Messina & Bell, 1991). Exogenous NGF increases the sensitivity of sensory neurons to capsaicin, probably by up-regulating capsaicin receptors (Bevan & Winter 1995;Hu-Tsai et al, 1996).…”