Cardiovascular and respiratory responses to chronic intermittent hypoxia in adult female rats

Souza GM, Bonagamba LG, Amorim MR, Moraes DJ, Machado BH.
Exp Physiol. 2014 Dec 16. doi: 10.1113/expphysiol.2014.082990

Volumes of research indicate that males are more susceptible to developing hypertension than premenopausal females. There is also data that shows that obstructive sleep apnea, a form of chronic intermittent hypoxia (CIH), leads to hypertension and that this apnea is more common in men than women. However, data linking this apnea to differences in men and women is scarce and a bit controversial.  In this study they looked at female rats exposed to CIH and examined changes in breathing patterns and blood pressure.
In this paper, they used a different CIH protocol than what was in some of the other papers I recently blogged. Here, they did 9 minutes of normoxia, and used nitrogen displacement to bring oxygen levels down to 6% for 40seconds, before being brought back to normoxia for another 9 minutes. This continued for 8hrs a day for 35 days. Rats were anesthetized and fitted with a femoral catheter to record arterial pressure. Respiratory activity was recorded 30 minutes after placing the rat inside of the plethysmographic chamber.
What they noticed was that CIH really messed up female rats’ cardiovascular system - they weighed less than controls (273 vs 347g), they had higher systolic (136 vs 129mmHg), diastolic (92 vs 86mmHg), and mean arterial pressures (111 vs 104mmHg), as well as increased heart rate (400 vs 376bpm). The systolic pressure was also more variable in CIH females. However, the dramatic changes seen in the cardiovascular system was not reflected in the respiratory system. Compared to controls, CIH rats didn’t have higher minute volume, tidal volume, or respiration frequency. However, short and long term variability was indeed higher in CIH rats.
Because respiratory and cardiovascular systems are coupled, they looked at how this relation changed between rat groups.  CIH rats had a stronger fall in MAP during deep breaths, and were more likely to have an apneic event after a deep breath than control rats, and the apnea lasted longer as well. They noted that their results were very comparable to the results of a different study on male rats that used the same protocol, but conflicted with another study in female rats that used a different CIH protocol which said that females DO NOT experience the strong changes seen in this paper. This suggests that females may have some protection against the changes, presumably due to differences in hormone levels, but that protection can be overcome by more severe CIH.  -DH

Neural control of the circulation: how sex and age differences interact in humans.

Joyner MJ, Barnes JN, Hart EC, Wallin BG, Charkoudian N.

Compr Physiol. 2015 Jan 1;5(1):193-215.

For reasons I am probably not at liberty to discuss, some of us in the lab have been discussing the differences in autonomic function between males and females. So I was pretty happy to see a review that had some of this information in it. As an added bonus, it discusses these differences mostly in humans (because we all need to focus on the transnational application of our basic science) with animal data where no human data was available.  Added bonus 2 is that this review comes from some reputable people, so it’s well-written and easy to understand.

In the review, they touched on a lot of topics, ranging from how (muscle) sympathetic nerve activity may be correlated with blood pressure in any given young man, but not from young man to young man, and not at all in young women. They also included various difficulties in experimental techniques (conduction speed differences between sympathetic and parasympathetic systems), neurotransmitter turnover times, and receptor availability/activity with modulation by different factors.  A couple of interesting things I learned were that even though estrogen is widely thought to prevent high SNA and blood pressure, conflicting data has also shown that high estrogen can sometimes correlate with high SNA, and that the age related changes seen in women after menopause will also occur regardless of menopause, and may just be related to age.  Confusing stuff.

Anyway, I liked this review a lot. I were running a lab, I would probably add it to the list of early required reading for new students. –DH

Chronic intermittent hypoxia increases sympathetic control of blood pressure: role of neuronal activity in the hypothalamic paraventricular nucleus.

Sharpe AL, Calderon AS, Andrade MA, Cunningham JT, Mifflin SW, Toney GM.

Am J Physiol Heart Circ Physiol. 2013 Dec;305(12):H1772-80.

This is a very slightly older paper from some of the same people I posted about last weekend. They were still looking to see how chronic intermittent hypoxia (CIH) could affect lumbar and renal sympathetic nerve activity (LSNA and RSNA), based on the existing theory that CIH causes hyperactivity of the chemoreflex, and the changes happen by way of the paraventricular nucleus (PVN). This time, the parameters of the CIH were: O2 levels were reduced to 10% for 6 minutes, 10x per hour, for 8 hours a day, for 7 consecutive days.

In this study they found that, compared to control rats, CIH rats had significantly higher MAP by day 3, with differences in heart rate not reaching significance. Rats exposed to 7 days of CIH had a greater reduction in MAP after ganglionic blockade (hexamethonium) than was seen in control rats, which indicated that CIH rats have increased sympathetic tone. Furthermore, muscimol inactivation of PVN caused greater reductions of lumbar SNA and MIP in CIH rats than controls, which also supports the idea that CIH rats have higher sympathetic tone. Furthermore, when CIH rats were given hypertonic saline directly in to the carotid artery, they showed a larger increase in LSNA (but not in RSNA) than control rats did. This suggests that there may be a greater LSNA responsiveness in CIH rats, and NOT a blunted/ceiling effect due to the higher SNA tone. This is also interesting on the basis that it adds more data to the idea of differential control of SNA. -DH