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.

Fig. 1.

A: representative coronal sections of the basilar artery at corresponding brain stem levels of Wistar (i) and spontaneously hypertensive rats (SHR; ii) at 2, 7, 26, 44, and 92 days of age [postnatal (P)]. B: age-related changes in basilar artery wall thickness (i) and the lumen-to-basilar wall thickness ratio (ii). According to our studies and those of Refs. , , , and , arterial pressure in the spontaneously hypertensive (SH) rat starts to diverge at 28 days and become hypertensive by 6 wk, times when morphological changes in the basilar artery have already occurred. Values are means ± SE. *P < 0.05, **P < 0.01.

Fig. 2.

A: photographs of the isolated arterially perfused rat brain stem before (i) and after (ii) cannulation of the basilar artery. Note the basilar artery was clamped just caudal to its bifurcation into the superior cerebellar arteries, as seen in ii. In i, the inset indicates the theta glass micropipette used for cannulation of the basilar artery. B: mean pressures ± SE within the basilar artery at different flow rates in SH (n = 7) and Wistar rats (n = 9). Comparison are between groups with unpaired Student's t-test. *P < 0.05, **P < 0.01.

Fig. 3.

Traces of perfusion pressure (PP), integrated phrenic nerve activity (PNA), raw thoracic sympathetic nerve activity (tSNA), and integrated tSNA (∫tSNA) in a Wistar (A) and SH (B) rat. LVA indicates timing of left vertebral artery (VA) occlusion. Both VAs indicate timing of simultaneous occlusion of both LVA and right VAs.

Fig. 4.

Percentage increase in tSNA absolute PP and absolute vascular resistance following bilateral VA occlusion in SHR and Wistar rats. Values are means ± SE. *P < 0.05, **P < 0.01.