Previous studies from our laboratory have demonstrated that the Y chromosome from the spontaneously hypertensive rat (SHR) is responsible for a significant portion of the elevated blood pressure and also produces an earlier pubertal rise in plasma testosterone. We performed the following studies to determine whether the SHR Y chromosome raises blood pressure by sympathetic nervous system responses as measured by adrenal chromogranin A and plasma and tissue catecholamines. Male SHR from the University of Akron colony were studied from 5 to 20 weeks of age. Blood pressure was measured by tail-cuff, tail artery cannulation, and aortic telemetry (Data Sciences); acute (air stress) and chronic (territorial colony) social stressors were compared; blood was collected for determination of plasma catecholamines; and adrenal glands were analyzed at 15 weeks for catecholamines. Rats with the SHR Y chromosome had higher blood pressure and plasma norepinephrine than those with the normotensive Wistar-Kyoto (WKY) Y chromosome. However, the SHR Y chromosome did not significantly change responsiveness to acute or chronic stressors. Phentolamine and clonidine prevented the stress responses. Adrenal chromogranin A levels were elevated 37% and 40% and adrenal norepinephrine content 29% and 100% at 4 and 10 weeks of age, respectively, in rats with an SHR Y chromosome compared with WKY. Chemical sympathectomy normalized blood pressure in all strains and significantly reduced norepinephrine (36% to 41%) in all strains except in WKY, which already had a normal blood pressure. In conclusion, the SHR Y chromosome appears to increase the chronic sympathetic nervous system. A potential mechanism could be a Y locus that influences chronic sympathetic nervous system activity, which may reinforce neurohumoral factors and structural components of the vessel wall, accelerating the development of hypertension.

The objective of this study was to determine whether the plasma norepinephrine (NE) increase in rats exposed to CO2 asphyxia was due to adrenal gland release or sympathetic nerve ending (SNS) release. Plasma NE was measured by high-performance liquid chromatography in hypertensive and normotensive rats using the following protocol: control session, CO2 exposure, N2 exposure, reserpine + CO2, and adrenalectomy + CO2. Four strains of male and female rats were used: spontaneously hypertensive rats, Wistar-Kyoto rats, and two congenic strains with different Y chromosomes. The same rats were used throughout the experiment ( n = 80). Blood pressure measured by aortic telemetry increased ∼50–60 mmHg in response to CO2 in all strains. CO2 increased NE 6–10× in all strains and both genders. N2 produced a significant increase in NE (73% of CO2 response). Reserpine significantly decreased (67%) plasma NE after CO2. Adrenalectomy did not significantly reduce the NE response to CO2. In conclusion, the increase in plasma NE after CO2 was associated with SNS release and not adrenal medullary release, was mainly due to hypoxia, and was not a specific response to CO2.

The objective of this study was to compare strain and gender differences in kidney and heart norepinephrine (NE) content and turnover rate in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR, SHR/a, and SHR/y). Our laboratory has shown that the Y chromosome has a significant effect on blood pressure in the SHR model of hypertension through the use of two new rat stains, SHR/a and SHR/y, to study the Y chromosome. SHR/a have a SHR autosomal genetic background with a WKY Y chromosome, whereas the SHR/y rats have a WKY autosomal genetic background with a SHR Y chromosome. Tissues were homogenized after alpha-methyl-DL-p-tyrosine injection and analyzed for NE. The male kidney NE content was significantly lower in the WKY compared with the SHR, SHR/y, and SHR/a. Kidney and heart NE content was significantly higher in females compared with males in all strains except the SHR/y. The WKY and SHR/y females had significantly lower kidney NE turnover rates, and the SHR and SHR/a females had significantly higher kidney NE turnover rates than strain-matched males. This study suggests both a strain and gender difference in sympathetic nervous system activity through noradrenergic neurotransmission.

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Our objective was to test the hypothesis that 1) a high Na (HNa, 3%) diet would increase blood pressure (BP) in male Wistar-Kyoto (WKY) and spontaneously hypertensive Y chromosome (SHR/y) rat strains in a territorial colony; 2) sympathetic nervous system (SNS) blockade using clonidine would lower BP on a HNa diet; and 3) prepubertal androgen receptor blockade with flutamide would lower BP on a HNa diet. A 2 x 4 factorial design used rat strains (WKY, SHR/y) and treatment [0.3% normal Na (NNa), 3% HNa, HNa/clonidine, and HNa/flutamide]. BP increased in both strains on the HNa diet (P < 0.0001). There was no significant decrease in BP in either strain with clonidine treatment. Androgen receptor blockade with flutamide significantly decreased BP in both strains (P < 0.0001) and normalized BP in the SHR/y colony. Neither heart rate nor activity could explain these BP differences. In conclusion, a Na sensitivity was observed in both strains, which was reduced to normotensive values by androgen blockade but not by SNS blockade.

Our objective was to test the hypothesis that nocturnal mean arterial pressure (MAP), heart rate (HR), and activity would be increased in 1) colony over individually caged rats and 2) the spontaneously hypertensive rat (SHR) Y chromosome strain (SHR/y colony) compared with Wistar-Kyoto (WKY) rats. MAP, HR, and activity were monitored using radiotelemetry. The nocturnal MAP rise expressed as the percentage change in MAP from light to dark was increased (P < 0.05) in the SHR/y colony. The SHR Y chromosome increased MAP in both the colony and caged groups compared with WKY (P < 0.001). The SHR/y colony animals spent 23% of a 24-h period at a MAP >120 mmHg, whereas the WKY colony animals spent 2% of a 24-h period in this range. The MAP of the SHR/y colony on clonidine was reduced (P < 0.001) to WKY baseline values. Activity but not HR was increased (P < 0.01) in the WKY and SHR/y colonies compared with caged animals. In conclusion, colony housing and the SHR Y chromosome increased MAP compared with individually caged housing.

The objective of this paper was to test the hypothesis that testosterone (T) raises blood pressure (BP), which is associated with increased coronary adventitial collagen, whereas the hemodynamic force of BP increases the coronary media:lumen ratio. Five treatment groups of spontaneously hypertensive rat (SHR) were established (n = 8-10 per group): controls; hydralazine (HYZ); castration; castration + HYZ; and castration + HYZ + T + captopril. At 12 weeks of age, the castrate + HYZ group was divided so that the mean BP was the same in both groups (162 mmHg). Both groups continued to receive HYZ treatment; however one group received T implants. Also, at 12 weeks of age the castrate + HYZ + T + captopril group received T implants. BP in the HYZ group was reduced compared with controls (192 mmHg vs 218 mmHg, p < 0.01). Castration lowered BP to 170 mmHg (p < 0.01) compared with controls. However, T implants increased BP by 15 mmHg (p < 0.02) in the castrate + HYZ group and by 44 mmHg in the castrate + HYZ + captopril group (p < 0.01). Captopril in combination with HYZ significantly reduced BP compared with controls but T replacement increased BP and coronary collagen deposition in spite of HYZ and captopril treatment.