Elevated vertebrobasilar artery resistance in neonatal spontaneously hypertensive rats

Abstract

There is a strong correlation between increased vertebral artery resistance and arterial blood pressure in humans. The reasons for this increased resistance at high systemic pressure remain unknown, but may include raised sympathetic activity. With the recent finding that prehypertensive spontaneously hypertensive (PHSH) rats, which have raised sympathetic nerve activity, but a blood pressure comparable to normotensive rat strains, we hypothesized that its vertebrobasilar vascular resistance would already be raised and, as a consequence, would exhibit a more responsive Cushing response (e.g., brain ischemia evoked sympathoexcitation and a pressor response). We report that PHSH rats exhibited a remodeling of the basilar artery (i.e., increased wall thickness and lower lumen-to-wall thickness ratio) that occurred before the onset of hypertension. In a novel in vitro vascularly isolated, arterially perfused brain stem preparation of PHSH rats of 4-5 wk of age, brain stem vascular resistance was raised by ∼35% relative to age- and sex-matched normotensive rats (P < 0.05). In the in situ arterial perfused working heart-brain stem preparation, occlusion of both vertebral arteries in the PHSH rat resulted in a significantly greater increase in sympathetic activity (57 vs. 20%, PHSH vs. control; P < 0.01) that triggered a greater increase in arterial perfusion pressure (8 vs. 3 mmHg, PHSH vs. control; P < 0.01) compared with normotensive rats. These data indicate raised vertebrobasilar artery resistance before the onset of hypertension in the PHSH rat. With the raised responsiveness of the Cushing response in the PHSH rat, we discuss the possibility of brain stem perfusion as a central nervous system determinant of the set point of vasomotor sympathetic tone in the hypertensive condition.

Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR

“…It should be noted that, in addition to the autonomic-immune drive, increased arterial pressure in the SHR is maintained by hypertrophy of peripheral arteries/arterioles (1). Differently from the ANG II-induced hypertension model, which is mostly related to neurogenic drive, SHR exhibits both early autonomic dysfunction (34) and vascular remodeling (3,8). These findings explain the conflicting data: normalization of arterial pressure in ANG II-induced hypertension (7,13,18) and hypertension attenuation in the SHR after chronic blockade of hypothalamic inflammation (14).…”

Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat

“…Interestingly, it has been shown that SHRs display increased vertebrobasilar artery remodeling and constriction (Cates et al . 2011), which may explain, at least in part, why the post‐stimulus overshoot in SHRs is maintained at a similar level before ganglionic blockade, despite operating at a hypoxic baseline level. Alternatively, it may be possible that SHRs have greater capacity to increase post‐stimulus brainstem oxygenation because they are hypoxic at rest or because they have slower O 2 consumption rates.…”

The sympathetic nervous system and blood pressure in humans: implications for hypertension

“…142 Intriguingly, narrower lumens and thicker vessel walls are observed in the vertebral and basilar arteries of the pre-hypertensive SHR compared with normotensive rats. 16,143 Similarly, in humans with hypertension, the vertebral arteries also appear to be narrowed and thickened and their vascular resistance is highly correlated with arterial pressure levels. 138 It has been proposed that triggering of SNA and systemic hypertension in response to inadequate cerebral blood flow is a protective mechanism to maintain perfusion.…”

“…138 It has been proposed that triggering of SNA and systemic hypertension in response to inadequate cerebral blood flow is a protective mechanism to maintain perfusion. 16,46,143,144 This warrants further exploration as a potential mediator of human hypertension.…”